60/491,258 filed July 31,2003, 60/493, 767 filed August 11,2003, 60/496,908 filed August 22,2003, and 60/501,832 filed September 11,2003, which are hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION Acquired Immune Deficiency Syndrome ("AIDS") is one of the most serious health threats confronting the human population today. AIDS is caused by a virus known as human immunodeficiency virus ("HIV") which presently includes HIV-1 and HIV-2. Over 40 million people are estimated to be living with HIV/AIDS.

Current projections suggest that an additional 45 million people will become infected between 2002 and 2010. So far, it is believed that more 25 million people have died from AIDS.

Since its emergence in the 1970s, HIV has produced a continually growing global pandemic, and it has, thus far, defied all attempts to produce an effective vaccine. Although a number of drugs have been developed to treat the disease, all have limited usefulness, serious side effects, a high potential for resistance, and none have been identified so far which can cure or prevent it. HIV vaccine research has expanded over recent years, but success so far using HIV-based components has been limited. See, e. g. , Graham et al., J. Inf. Disease., 166: 244-252,1992 ; Belshe et al., J.

Inf Disease., 183: 1343-52,2001 ; Horton et al., J. Virol., 76: 7187-7202,2002 ; Gilbert et al. , Vaccine, 21: 2933-2947,2003.

DESCRIPTION OF DRAWINGS FIG. 1 (A-C). Comparison of cells from vaccinated versus non-vaccinated subjects, infected with the macrophage (CCR5) tropic HIV. A. A comparison of the mean + standard error measurement of the vaccinated versus non-vaccinated groups in cultures without autologous serum. (*, p<0.05) B. A comparison of the mean +

standard error measurement of the vaccinated versus non-vaccinated groups in cultures with autologous serum (*, p< 0.05 ; **, p<0.01). C. Comparison of the mean + standard error measurement of cells from vaccinated versus non-vaccinated subjects, infected with the T-cell (CXCR4) tropic HIV.

DESCRIPTION OF THE INVENTION The present invention provides methods and compositions for treating and/or preventing HIV infection in a subject in need thereof. It features the use of poxviruses for therapy, prophylaxis, and diagnosis of HIV, as well as for any other medical or veterinary use associated with HIV and homologous viruses. The invention also provides for the use of poxviruses in the discovery of new agents to prevent and/or treat HIV infection.

A poxvirus or a component thereof, can be used to treat and/or prevent infection caused by any virus, preferably a lentivirus, such as HIV, that uses a CCR5 chemokine receptor for its infection of cells. This includes, but is not limited to, e. g., HIV-1 (e. g. , clades A, B, C, D, and G, R5 and R5X4 viruses, etc. ), HIV-2 (e. g., R5 and R5X4 viruses, etc. ), simian immunodeficiency virus (SIV), simian/human immunodeficiency virus (SHIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) (Wright et al., Vet. Res. C07nmun., 26: 239-50, 2002), HTLV-1, HTLV-2, etc. It can be used as a vaccine, adjuvant, therapeutic agent, in combination with other agents, or in any suitable manner to treat and/or prevent such infections.

Any poxvirus can be used in accordance with the present invention, including, but not limited to, orthopoxvirus, parapoxvirus, avipoxvirus, capripoxvirus, leporipoxvirus, suipoxvirus, etc. Orthopoxvirus, include, e. g., buffalopox, camelpox, cowpox, monkeypox, rabbitpox, raccoon pox, tatera pox, canarypox, fowlpox, vaccinia, variola, and vole pox. Vaccinia virus is the prototype of the genus Orthopoxvirus for the desired effects, but other poxviruses can be used in its place.

Thus, although the disclosure below may be written in terms of vaccinia, any poxvirus can be utilized in accordance with the present invention.

Vaccinia is a double-stranded DNA (deoxyribonucleic acid) virus. All strains, derivatives, variants, mutations, naturally-occurring strains, genetically-engineered, recombinant, etc. , of vaccinia can be used in accordance with the present invention.

For more information on vaccinia and other poxvirus, see e. g., Virology, Fields et al., Volume 2, Chapters 74-75, Raven Press, 1990.

An amount of the poxvirus, such as vaccinia virus, can be administered to a subject in a quantity which is effective to achieve a therapeutic or prophylactic effect.

The term"poxvirus, ""vaccinia virus, "etc., indicates that the virus (genome and protein coat) is administered to a subject. It can be administered in any effective form, including, e. g. , as a live virus, as a live-attenuated virus, as a replication- deficient virus, as a viral extract not having any live viral particles, etc. Compositions comprising a poxvirus can be produced and utilized in any suitable manner, including, e. g. , recombinant, naked DNA technology, etc.

The term"treating"is used conventionally, e. g. , the management or care of a subject for the purpose of combating, alleviating, reducing, relieving, improving, eliminating, etc. , one or more signs or symptoms associated with HIV infection.

Treatment includes delaying the progression of HIV and its associated symptoms, thereby extending the life expectancy of an infected subject, and/or delaying or reducing the onset of symptoms associated with HIV infection. Treating can involve inhibiting, reducing, diminishing, etc. , the replication and other events in the life cycle of the HIV virus.

The term"preventing"HIV infection indicates that a subject's susceptibility to HIV infection upon exposure to the virus is reduced or diminished as a result of the administration of the poxvirus. The subject's resistance to HIV infection is increased or improved by the poxvirus treatment since s/he is less likely to become infected by the virus. Any amount of improved resistance is useful, e. g. , greater than 5-fold, greater than 7-fold, greater than ten-fold, etc. , and any such improvement can be regarded as prevention.

A poxvirus, or component thereof, used in the present invention can be prepared routinely, or obtained from commercial sources. Attenuated strains are preferred. Attenuated strains are less able to cause disease, and are considered less virulent and weakened as compared to strains that are not attenuated.

Any strain of vaccinia virus, or components thereof, can be utilized to achieve a prophylactic and/or therapeutic effect, including, but not limited to, e. g. , strains available from the ATCC, ECACC, or other virus collections, replication-competent, replication-deficient, non-replicating, attenuated strains, modified vaccinia Ankara (MVA), vaccinia virus Ankara, NYVAC (ATCC No. VR-2559) replication-deficient vaccinia viruses, W Copenhagen, W Western Reserve, W Wyeth (ATCC No.

VR325), Elstree, strains deficient in vCCI (Reading et al., J. ! o/., 170: 1435-42, 2003), and/or vGF, strains comprising one or more copies of the 17K myristyloprotein, poxvirus strains, CCR5-dependent poxvirus strains, etc. DryvaxOO, a vaccinia (smallpox) vaccine currently licensed in the United States, is a lyophilized, live-virus preparation of infectious vaccinia virus (Wyeth Laboratories, Inc. , Marietta, Pennsylvania). Other strains which have been used include, but are not limited to, e. g., Lister, Bordeaux, Paris, Massachusetts 999, New York, Temple of Heaven, Patwadangar, Ikeda, Bern, Vienna, Bohemia, Finland, Hamburg, Budapest, Aosta, Spain, Sweden, B-51, Tashkent, EM-63, LE-IVP (Lister), etc. See, also, Smallpox and its Eradication, Fenner et al. , WHO, Geneva, 1988, e. g. , Chapter 11. Other strains include, e. g. , MVA-BN (modified vaccinia Ankara-Bavarian Nordic) (ECACC V00083008; WO 02/42480), MVA-Vero (US 20030013190), MVA-NH, MVA 572 (ECACC V94012707), LC16m8, and ACAM1000 (ATCC Deposit No. PTA-3321; WO 02/085411). Any strain of canarypox can be utilized as well, including attenuated canarypox virus such as, e. g. , ALVAC (ATCC No. VR-2547).

Deposited strains also include, e. g. , ATCC Nos. VR-117 (CL), VR-118 (Lederle-Chorioallantoic), VR-119 (WR (Mouse Neurotropic), VR-1354 (WR (NIH TC-adapted), VR-1431 (P-4), VR-1441 (IHD-W), VR-1508 (Modified vaccinia virus Ankara (MVA)), VR-1536 (New York City Department of Health Laboratories (Wyeth-calf adapted) ), VR-1549 (Elstree (Lister Vaccine) ), VR-156 (IHD), VR-2010 (AS), VR-2031 (Vtk-79), VR-2034 (S-variant), VR-2042 (vP-7), VR-2043 (vP-9), VR-2292 (SLZ103 [recombinant Vaccinia virus (WR)]), VR-2379 (Rpmuhr+ [recombinant of Utrecht strain Rpuhr23]), VR-2589 (VVtml : hPCl [recombinant Vaccinia virus, in vitro construct]), VR-302 (Brighton), VR-3103 (IHD-W Dts 16 [Vaccinia ts-mutant] ), VR-3109 (IHD-W Dts 46 [Vaccinia ts-mutant]), VR-3110 (IHD-W Dts 2 [Vaccinia ts-mutant] ), VR-3113 (IHD-W Dts 17 [Vaccinia ts-mutant] ),

VR-3121 (IHD-W Dts8 [Vaccinia ts-mutant] ), VR-3126 (IHD-W Dts 33 [Vaccinia ts- mutant] ), VR-3129 (IHD-W Dts 48 [Vaccinia ts-mutant] ), VR-3130 (IHD-W Dts 4 [Vaccinia ts-mutant] ), VR-3139 (IHD-W Dts 50 [Vaccinia ts-mutant] ), VR-3142 (IHD-W Dts 10 [Vaccinia ts-mutant] ), VR-3144 (IHD-W Dts20), VR-3147 (IHD-W Dts 35 [Vaccinia ts-mutant] ), VR-3148 (IHD-W Dts 40), VR-3154 (IHD-W Dts71 [Vaccinia ts-mutant] ), VR-3160 (IHD-W Dts52 [Vaccinia ts-mutant] ), VR-3161 (IHD-W Dts 57), VR-3165 (IHD-W Dts 77), VR-3166 (IHD-W Dts 82), VR-3169 (IHD-W Dts97 [Vaccinia ts-mutant] ), VR-3175 (IHD-W Dts 78 [Vaccinia ts- mutant] ), VR-3176 (IHD-W Dts 83 [Vaccinia ts-mutant] ), VR-3178 (IHD-W Dts 93 [Vaccinia ts-mutant] ), VR-3196 (IHD-W Dts 95 [Vaccinia ts-mutant]), VR-587 (Yaba monkey tumor virus deposited as Yaba monkey tumor virus, Yatapoxvirus (Roswell Park-Yohn)), VR-838 (Raccoonpox virus, Orthopoxvirus (Herman)).

A vaccinia virus is a preferred poxvirus in accordance with the present invention, but other poxviruses can also be used to treat and/or prevent HIV. For example, any poxvirus which expresses a gpl20-like or TAT-like polypeptide, or which depends on CCR5 for entry into a cell can be used in accordance with the present invention.

Vaccinia virus can be administered to subjects according to any regimen which is effective for treating and/or preventing HIV infection. The particular dosages (i. e. , effective amounts), and number and frequency of vaccinations can be determined routinely.

An effective amount of virus, or virus component, is the quantity of virus, or virus component, which is useful to achieve the desired purpose, e. g. , to treat and/or prevent HIV infection. These amounts can be determined routinely. Effective amounts can be the same or less than the amounts currently used to achieve pox immunity with a pox vaccine. For example, Dryvax is commonly used at a potency of 100 million pock-forming units (pfu)/ml for primary vaccination for smallpox.

Any effective amount can be used in accordance with the present invention, e. g., about 105-109 pfu/ml. The quantities of the particular virus which is utilized can be adjusted and determined routinely, e. g. , to eliminate or reduce adverse reactions associated with the virus, as well as depending on the health of the patient receiving the treatment.

The specific dose level and frequency of dosage may vary, and can depend upon a variety of factors, including the activity and state of the specific poxvirus, e. g., whether it is live, heat-inactivated, attenuated, etc. , its metabolic stability and length of action, rate of excretion, mode and time of administration, and the age, body weight, general health, gender, diet, and particular condition of the subject undergoing treatment or prevention.

Poxvirus can be administered in any form by any effective route, including, e. g. , oral, parenteral, enteral, intraperitoneal, topical, transdermal (e. g. , using any standard patch), ophthalmic, nasally, local, non-oral, such as aerosal, spray, inhalation, percutaneous (epidermal), subcutaneous, intravenous, intramuscular, buccal, sublingual, rectal, vaginal, intra-arterial, mucosal, and intrathecal, etc. It can be administered alone, or in combination with any ingredient (s), active or inactive.

Any subject can be administered a poxvirus in accordance with the present invention, including subjects who have been exposed to HIV, but have not yet developed HIV infection, as well as subjects who have progressed to one or more of the clinical symptoms of HIV infection (e. g. , AIDS). In addition to treating and/or preventing HIV infection in humans, a poxvirus can be used to treat other organisms (e. g. , non-human primates, cats, etc. ) infected with HIV, or HIV-related viruses, such as SIV, SHIV, or FIV. Thus, subjects who can be treated include, e. g., mammals, humans, monkeys, apes, chimpanzees, gorillas, cats, dogs, mice, rats, etc.

Subjects, who have been exposed to HIV virus, or who are at risk for developing the disease, are particular candidates for poxvirus vaccination. For instance, a subject who has not yet tested positive, but has been exposed to HIV, can be administered vaccinia virus as a prophylactic/therapeutic approach. Individuals at high-risk for the disease, such as sexually-active individuals, subjects in parts of the world where HIV infection is high, subjects receiving blood and/or other invasive medical procedures, can also receive vaccination to increase their resistance to HIV infection.

In addition to administering the whole poxvirus, components of it can also be administered in accordance with the present invention. By the phrase"component,"it is meant any part of the virus, which is less than the whole virus genome, including

particular nucleic segments of its genome, as well as any product which is produced using the viral genome. This includes modifications to polypeptides encoded for by the virus.

Components include polypeptides comprising the virus, such as envelope proteins, processing enzymes, structural proteins, nucleic acid synthesis enzymes, glycoproteins, carbohydrates, lipids, antigens or antigenic fragments of the virus, etc.

Also included are nucleic acid fragments of the whole genome, including fragments comprising complete gene sequences, control sequences, etc.

Components includes one or more of the over about 198 open reading frames (ORF) and about 268 genes that have been identified in vaccinia and other poxvirus.

Components include one or more of the genes and products thereof described in, but not limited to, Antoine et al., Virology, 244: 365-396,1998, and Goebel et al., Virology, 179 (1) : 247-266,1990 for vaccinia virus; Willer et al., Virology, 264 (2): 319- 43,1999 for Leporipoxvirus Shope fibroma virus (SFV); Cameron et al., Virology, 264 (2): 298-318,1999 for myxoma virus; Shchelkunov et al., Virology, 297 (2): 172- 94,2002 for monkeypox virus; Shchelkunov and Totmenin, Virus Genes, 9 (3): 231- 45,1995 for variola, Massung et al., Virology, 201 (2): 215-40,1994. For example, the polypeptide coding for the 17K myristylprotein, and which has amino acid sequence homology to gpl20, can be used alone or in combination with other antigens, etc. , in accordance with the present invention. See, e. g. , Antoine et al., 1998 ; Barrett et al., Seminars in Immunol., 13: 73-84,2001. See, also Tables 1 (from Goebel et al., Virol., 179: 247-266,1990) and 2 (from Antoine et al., Virol., 244: 365-396,1998). Moreover, one or more of the aforementioned genes and open reading frames can be deleted from a vaccinia virus, e. g. , to eliminate a toxic or other undesirable effect of an administered virus.

A useful composition can comprise one of the components of a poxvirus, including one or more of the components described in Tables 1 and 2. These can be individual purified and then combined into a therapeutic or prophylactic composition, or extracts can be prepared from viral particles and treated as desired. The individual components can be purified from the viral particles, or produced recombinantly, e. g., where a target gene is cloned, expressed in a host cell under conditions where the polypeptide is manufactured by the cell, and separating and purifying the polypeptide

accordingly to conventional methods. Components can also be administered as naked DNA. See, e. g. , U. S. No. 6,413, 942.

The therapeutic and/or prophylactic effect achieved with the poxvirus can be independent of an immunological response to it. For example, the purpose of ordinary smallpox vaccination is to elicit an immune response by the host. This response is both humoral and cellular, involving the generation of specific antibodies and immune cells (such as T-cells, cytolytic or cytotoxic T lymphocytes, etc. ) which protect a host from future invasion by the smallpox virus. While the present invention is not bound by any mechanism through which the poxvirus achieves its therapeutic and/or prophylactic effect, it can be mediated through a pathway separate from the immune response and not require cellular or humoral immunity. For example, poxvirus, or a component thereof, can directly block or inhibit the ability of a HIV to infect a cell. In this respect, the poxvirus, or component of it, acts as an antagonist, blocker, etc., of HIV's ability to infect target cells. HIV usually activates a G-protein- coupled signal pathway cascade. Poxvirus can interfere with this pathway or modify it such a way that the cell is more difficult to infect, thereby increasing its resistance to the HIV virus. Consequently, the effective amounts of a poxvirus, or component thereof, can differ from the amounts that are ordinarily used when the objective is to achieve a humoral and/or cellular immune response.

Vaccination with vaccinia can be associated with adverse reactions. Those at highest risk include, e. g., pregnant women, immunocompromised patients (e. g. HIV- positive) ; and persons who have atopic dermatitis or eczema. Strains which are attenuated or otherwise modified to reduce adverse effects are especially useful in accordance with the present invention, e. g. , for administration to persons at risk for adverse effects.

Modified strains of vaccinia can be utilized that are deficient, mutated, engineered, etc. , in one or more of the about 198 open reading frames (ORF) and/or about 268 genes that comprise vaccinia (depending on the strain or variant). In addition, genes can be inserted into vaccinia, including, one or more copies of a vaccinia gene of interest (e. g., 17K myristylprotein, vCCI), and/or genes coding for all or part of an HIV proteins, such as gpl20 or gp40.

The present invention also provides methods of treating and/or preventing HIV infection in a subject in need thereof, comprising, e. g. , administering multiple doses of a poxvirus, or components thereof, to a subject, wherein each dose is administered at a time interval from the previous dose, and are effective to maintain a therapeutic effect, or to maintain protection against HIV infection. As discussed above, a dose of the poxvirus, or component thereof, is the amount of virus which is useful for accomplishing the therapeutic or prophylactic effect. More than one dose can be administered to the subject in order to maintain the therapeutic efficacy of the treatment, or to maintain protection against HIV infection. For example, smallpox immunization is usually achieved by a single vaccination with a booster every 5-10 years. To maintain protection against HIV, more frequent vaccination can be used, e. g. , multiple times a year, at least twice a year, yearly, every two years, every three years, more than once every less than five years, more than once every less than ten years, etc. The periods between the separate and sequential vaccinations can be referred to as"time intervals. "These intervals can be spaced apart by any desired time period which is effective to maintain protection or therapeutic efficacy in treating an infected subject. The intervals can be predetermined or preset, where they are already specified, or they can be determined by monitoring the progress of a subject, e. g. , using blood serum to measure poxvirus antibody titer, or HIV titer in an infected subject. The frequency of vaccination utilized to achieve efficacy may vary depending upon multiple factors, including, e. g. , person-to-person variations in the immune system, the stage of HIV infection, the potency of the virus or vaccine, etc, and may be as often as every 3 months to once every 5 years.

The present invention also provides methods of treating and/or preventing lentivirus infection in a subject in need thereof, comprising: administering an effective amount of a poxvirus or component thereof, wherein said amount is effective to treat and/or prevent lentiviral infection, with the proviso that a lentivirus nucleic acid, such as HIV, is not contained in the poxvirus genome. This excludes, e. g. , a poxvirus which is utilized as a vector to administer HIV nucleic acid, such as when HIV nucleic acid is inserted into the poxvirus genome.

The present invention also provides methods of identifying a component of a poxvirus, or a poxvirus-associated agent, which interferes with HIV infection, and

components and agents identified thereby. Interfering with HIV infection indicates that the agent or component decreases, reduces, diminishes, lessens, etc. , the ability of a susceptible cell or organism to become infected with HIV virus as compared to the same cell or organism in the same conditions, but in the absence of the agent or component. Interference with HIV infection can occur at any level, e. g. , by blocking the ability of HIV to attach to its receptor (s) on a cell, by blocking the ability of HIV to be taken into a cell, by blocking viral function once inside the cell, by blocking viral infection, etc. The invention is not limited by the mechanism through which HIV interference is achieved. By interfering with HIV infection, the cell's or organism's resistance to HIV is increased.

These methods can involve one of more of the following steps in any effective order, e. g. , (1) contacting a cell or organism which is susceptible to HIV infection with poxvirus, or a component thereof, or a poxvirus-associated agent, (2) contacting said cell or organism with HIV under conditions effective for said HIV to infect said cell or organism, and, (3) (a) determining whether said cell or organism is resistant to HIV infection, whereby said agent is identified as interfering with HIV infection, or (3) (b) identifying the poxvirus, or component thereof, which confers resistance to HIV infection. The term"organism"as used herein indicates a fully-gestated animal.

The method can also involve a step of identifying the poxvirus, or a component thereof, as the agent which confers resistance to HIV infection.

Identifying the poxvirus, or component thereof, which confers resistance to HIV infection, indicates that the poxvirus is positively determined or ascertained to provide protection or resistance against HIV. This indicates a positive result in the method.

Agents can be tested for their ability to interfere with HIV infection in any suitable system, including whole animals and cell culture. Animal cells useful in the present invention are those which are susceptible to HIV infection, i. e. , they are capable of being infected by the HIV virus. They can be naturally-susceptible, or genetically-engineered to confer susceptibility, e. g. , by expressing HIV receptor (CCR5, CD4, etc. ), or by grafting on the human immune system. Any methods for testing whether a cell or organism is infected with HIV can be used, e. g. , measuring

anti-HIV antibody titer (e. g., gpl20 antibodies), reverse transcriptase protein or nucleic acid, or any other polypeptide or nucleic acid.

Any suitable animal model for testing the efficacy and dosage of a poxvirus (or component thereof) can be used in accordance with the present invention. These include, but are not limited to, e. g. , SCID mice reconstituted with human immune system components (e. g. , peripheral blood lymphocytes) [e. g. , Zhang et al. , Proc.

Natl. Acad. Sci., 93: 14720-14725,1996, using SCIC. bg mice], chimpanzees infected with HIV-1, macaque monkeys infected with SIV, HIV2, or chimeric SIV/HIV [e. g., Johnson, Curr. Opin. Imnzu7aol., 8 (4): 554-560,1996], cats infected with feline immunodeficiency virus, HIV-1 transgenic mouse model [e. g., mice which have integrated molecular clone pNL4-3 containing 7.4 kb of the HIV-1 proviral genome deleted in the gag and pol genes (Dickie et al., Virology, 185: 109-119,1991 ; transgenic mice carrying an HIV provirus, optionally with deletion of one or more HIV genes (Tinkle et al., J. Clin. Invest., 100 (1) : 32-9,1997)], HIV-1 transgenic rat model, human CD4 transgenic rat model, horse infected with EIAV, sheep infected with visna virus, goats infected with CAEV, etc. See, also, The Retroviridae, J. A.

Levy, ed., Plenum Press, 1993, e. g., Chapters 3,4, and 5.

A vaccinia virus-associated agent is any substance which is produced in response to a vaccinia infection, or in response to inhalation, injection, ingestion, etc., of any vaccinia virus, or component thereof. This substance can be present in a culture medium in which cells exposed to vaccinia have been cultured, or can be present in blood serum when harvested from an organism exposed to vaccinia. The present invention provides compositions which comprise such substances.

The invention also provides combinations of pharmaceutical agents for treating and/or preventing HIV, e. g. , poxvirus, or a component thereof, and an agent which is used to treat HIV, such as a protease inhibitor or a reverse transcriptase inhibitor. Examples of the latter classes of drug, include, but are not limited to, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, AZT, ddI, ddC, ddT, 3TC, nevirapine, delavirdine, etc.

The active agents can be present in the same dosage unit (e. g. , a composition), or can be used as separate dosage units.

In addition, a poxvirus, such as vaccinia, can be administered in combination with HIV nucleic acid. The HIV nucleic acid can be physically joined to the poxvirus genome, or it can be administered as a separate component. For example, HIV nucleic acid (e. g. , coding for gpl20 or another viral antigen) can be administered at the same time as a poxvirus, but as a physically separated entity, or it can be administered at subsequent times after receiving only poxvirus) as part of a regimen for treating and/or preventing HIV infection.

The present invention also provides methods of making a poxvirus composition for conferring resistance to HIV infection or treating HIV infection,, comprising, one or more of the following steps in any effective order, e. g. , preparing a composition comprising poxvirus, or a poxvirus component thereof, and/or identifying that the poxvirus, or component thereof, confers resistance to, or treats, HIV infection. As mentioned earlier, the identifying step indicates obtaining a positive result in finding that the poxvirus (e. g. , vaccinia), or component thereof, provides resistance, protection, treatment, etc. , against the HIV virus.

The preparation of a poxvirus composition can be carried out routinely, e. g., according to conventional methods used for vaccine manufacture. Preparing includes culturing poxvirus, isolating poxvirus, putting poxvirus into a form suitable for administration (oral, injection, nasal, etc. ), making poxvirus components recombinantly, etc. The prepared poxvirus (or components of it) can be assayed for its ability to confer resistance to HIV infection to an organism challenged with it or provide a therapeutic effect. By this, it is meant that a sample of the prepared composition is tested to determine its titer, concentration, potency, etc. , in making a subject, to whom it is administered, "resistant"to the HIV virus, or for its therapeutic effect. The assay step can be carried out on every batch, or only selected batches, etc.

A purpose of this step is, e. g. , to confirm that the manufactured poxvirus possesses an anti-HIV activity for which it is to be administered. Any suitable assay or testing method can be utilized, e. g. , in vitro methods of evaluating its efficacy or potency.

For instance, the determining step can involve, e. g. , challenging said organism, or cells derived from it, with infectious HIV, and detecting the expression in said organism or cells of gpl20, HIV reverse transcriptase, p24, infectious HIV particles, and/or HIV nucleic acid. By"challenge"it is meant the cells or organism are placed

in contact wit the HIV virus under conditions which are effective to become infected by it. These conditions will vary, depending upon how the assay is specifically accomplished.

When poxvirus is administered to a host, it can elicit a cellular response that is responsible or associated with the host's subsequent ability to resist HIV infection and/or treat HIV infection. This response can be measured, and used as index or marker to assess the efficacy of the poxvirus, and/or to determine effective amounts of it for the desired purpose (i. e. , treating or preventing HIV infection). The appearance of one or more of the following"markers"can be modulated (e. g., elicited, stimulated, down-regulated, up-regulated, etc) by poxvirus, and associated with its anti-HIV effect, thereby making the marker useful as an indicator of poxvirus efficacy. By the term"marker,"it is meant any measurable response to a poxvirus, including its effect on HIV's ability to infect and replicate in a cell, as well as on the host's immune system and the cells which comprise it. These markers, include, but are not limited to, one or more of the following agents, activities, responses, pathways, etc.: - CD4 expression, e. g. , measuring the amount of CD4 present in a cell-type that is susceptible to HIV infection - HIV coreceptor expression, e. g., CCR5 or CXCR4 chemokine receptor, including its cell-surface expression - Cytokine receptors - Virus-specific CTLs (cytolytic or cytotoxic T-cells, including CD8+ T-cells) which are capable of lysing HIV infected cells (cells can be co-infected with poxvirus and HIV, or infected by HIV alone) - CD8 cells - Cytokines, including mediators and regulators of innate immunity, such as interferons, type I interferon, interleukins, interleukin-15, interleukin-12, tumor necrosis factor, interleukin-l, interleukin-6, interleukin-10, etc.; and mediators and regulators of specific immunity, such as interleukins, interleukin-2, interleukin-4, transforming growth factor-beta, interferon-gamma, lymphotoxin, interleukin-5, etc.

- Chemokines (a large family of structurally homologous cytokines, that, e. g., stimulate leukocyte motility and directed movement), including, but not limited to,

the C-C and C-X-C families. Examples of chemokines, include, but are not limited to, e. g. , interleukin 8, Gro, platelet basic protein, epithelial-derived neutrophil attractant 78, platelet factor 4, interferon-gamma-induced protein 10, stromal cell- derived factor-1, monocyte chemotactic proteins 1, 2, and/or 3, RANTES, monocyte inflammatory protein 1-alpha and 1-beta ("MIP"), eotaxin, lymphotaxin, etc.

- Thl/Th2 phenotype and cytokine secretion pattern. Effector T-cells (e. g., CD4+ helper T-cells) can be categorized, on the basis of the cytokines they secrete, into Thl and Th2 cells. Thl cells secrete, e. g. , interferon-gamma, lymphotoxin-alpha, TNF-beta, IL-2, IL-10, and CCR5 ligands, such as RANTES and MIPS. Th2 cells secrete, e. g. , IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, etc. Thl and Th2 cells also include resting, but polarized T-cells (i. e., committed to a Th type). In addition to cytokine production profiles, there are a number of cell surface markers that can be used to differentiate between Thl and Th2 subtypes. For example, Thl cells express both components of IL-12 receptor chains (betal and beta2), while Th2 cells exhibit IL- 12R-betal. Th2 cells exhibit both IFN-gamma receptor chains (a and b), while Thl cells express IFN-gamma-R-alpha. Th2 cells appear to express a fully functional IL-1 receptor, and ST2L/T1, an IL-lR-like molecule, is found on Th2 cells. Chemokine receptors CXCR-3 and CCR-5 are also characteristic of Tlil cells, while CXCR-4, CCR-3, CCR-4, CCR-7 and CCR-8 are associated with Th2 cells. CD30, a member of the TNF superfamily, is associated with Th2 cells. The Thl/Th2 pattern can be polarized by poxvirus administration, resulting in a phenotype that favors the secretion, etc. , of cytokines that inhibit HIV infection and/or render cells resistant to infection. One or more of the aforementioned molecules can be utilized as markers of poxvirus efficacy - Antibodies that specifically recognize HIV, e. g. , neutralizing antibodies - Antibodies that specifically recognize poxvirus - Complement control protein. Vaccinia virus encodes a secreted complement control protein (VCP, 35-kDa) protein with sequence homology to the SCR- containing complement control protein superfamily. It binds C3b and C4b, and interferes with the complement cascade by providing cofactor activity for the cleavage of C3 and C4 by factor I, and by accelerating the decay of the C3 converse of both the alternative and, more effectively, the classical pathway of complement

activation. VCP may suppress the complement system or their receptor expression, rendering the host less susceptible to the complement-enhancement of HIV infection - Activation state of a cytokine receptor, e. g., CCR5 receptor or other HIV chemokine coreceptor. For example, poxvirus can interfere with CCR5 activation after HIV binding, e. g. , by modulating tyrosine kinase feedback pathways - One or more of the vaccinia proteins listed in Tables 1 and 2. This includes any poxvirus-encoded protein that specifically interferes with CCR5/CD4/gpl20 interactions, including, e. g. , vaccinia encoded CC chemokine binding proteins and/or IFN-gamma receptor-like protein - RNA interference with HIV expression/replication in infected cell - Alpha-defensins 1,2, and/or 3 - Soluble factors including those produced by CD8+ lymphocytes and sometimes referred to as CAF - Interference with the HIV life cycle, including viral entry, import into the host cell nucleus, viral integration into host genome, Rev-dependent and Rev- independent transport from the host nucleus, replication, gene expression, RNA splicing, etc - Inhibiting HIV replication, including its ability to make copies of itself in the cell, and for productive viral particles to be extruded into the blood - Inhibiting the ability of HIV to infect a cell, e. g. , to bind to CD4 and/or its coreceptor, for the envelope protein to fuse with the host cell membrane, etc.

- Modulating gene expression of the HIV virus, including modulating regulatory genes (e. g. , tat and rev), accessory genes (e. g. , vif, vpu, vpr, and nef), structural genes (e. g. , gag, pol, and env), inner core polypeptides (e. g. , gag, pl7, p24, p7, and p9), viral enzymes (pol, reverse transcriptase, protease, and integrase), and envelope proteins (e. g., env, gpl20, and gp41). The phrase"gene expression"is used broadly to mean any step in the pathway from viral RNA to protein synthesis, and therefore includes all regulatory processes, transcription, translation, polypeptide processing, etc.

- Modulating activity of a HIV encoded polypeptide, including, tat, rev, vif, vpu, vpr, nef, gag, pl7, p24, p7, p9, pol, reverse transcriptase, protease, integrase, env, gp120, gp41, etc.

- Modulating viral regulatory sequences, such as RRE, cis-acting repressive sequences (CRS), and inhibitory/instability RNA sequences (INS) - Any cell or tissue of the immune system, including, but not limited to, lymphocytes, B lymphocytes, T lymphocytes, helper T cells, cytotoxic (or cytolytic) T cells ("CTL), natural killer (NK) cells, naive T cells, memory T cells, CD4+ helper T cells, CD8+ CTLs, monocytes, macrophages, antigen-presenting cells (APCs), dendritic cells, granulocytes, etc.

The present invention also provides kits comprising a poxvirus. For example, a kit for preventing HIV infection, comprising: an effective amount of a poxvirus, and instructions for administering an effective amount of said poxvirus to a subject to prevent HIV infection; and a kit for treating HIV infection, comprising: an effective amount of a poxvirus, and instructions for administering an effective amount of said poxvirus to a subject to treat HIV infection. The instructions can provide any information that is useful for directing the administration of the poxvirus for the desired purpose.

The present invention also provides methods of advertising, licensing, selling, purchasing, etc. , a poxvirus for the purpose of treating and/or preventing HIV infection. Methods can comprise, one or more of the following steps in any effective order: e. g. , displaying information (a) comprising instructions for administering a poxvirus for treating and/or preventing HIV infection or (b) comprising a description of the use of poxvirus for treating and/or preventing HIV infection, in a printed or computer-readable medium (e. g. , on the Web, Internet, personal computer, server, etc); offering for sale a poxvirus for treating and/or preventing HIV infection in a printed or computer-readable medium; accepting an offer to purchase poxvirus for said use in a printed or computer-readable medium.

EXAMPLES The following experiments were performed in the laboratory of Dr. Beda Brichacek and Dr. Michael Bukrinsky of the Department of Microbiology and Tropical Medicine, The George Washington University, Washington D. C. 20037.

Methods Subject selection and specimen collection.

Twenty subjects were chosen for inclusion in the study. Ten subjects had been immunized with vaccinia within the previous 3 to 6 months, and ten subjects had never been immunized with vaccinia. All subjects were healthy and had a negative HIV test within the previous year. No subjects of northern European descent were used in order to avoid the potentially complicating factor of including a subject who might be homozygous for the CCR5-delta32 mutation. Two tubes of heparinized blood and 1 serum separator tube were collected. All blood samples from all subjects were drawn within 6 hours of each other, and were immediately processed to separate the PBMCs using standard methods of Ficoll-Hypaque centrifugation.

Cell culture preparation.

PBMCs were centrifuged at 1200 rpm for 11 minutes and resuspended in RPMI tissue culture medium + 10% fetal calf serum +10 ag/ml gentamicin at a concentration of about 1-3 x 106cells/ml with a final concentration of 2 x 106 cells/culture. Cell cultures were incubated in a C02 incubator. On the second day, one of the utilized strains of HIV was mixed with either culture medium or serum from each individual subject and incubated on ice for 7 hours after which 175 jul of each mixture was added to the autologous cell cultures. The next day 1 ml of cell culture media was added and the cultures were incubated for 5 hours to dilute the viral inoculum and to allow the virus to detach. The supernatant was carefully aspirated and 1 ml of fresh media was added before the cultures were spun down at 1000 rpm for 7 minutes. The supernatant was again aspirated and 2 ml of fresh media was added to each culture. 150 al of supernatant for RT analysis was aspirated from each culture tube on days 2,5, 8 and 10, and if needed, up to an additional 1 ml was aspirated and replaced with fresh media. On day 2, PHA was added to the tubes of

culture series F to act as a cell activator. On day 5,2 ml of supernatant was removed from each of tubes of culture series F and replaced with 2 ml media + human serum + IL-2.

Reverse Transcriptase (RT) analysis.

The measurements of viral replication were performed by standard RT assays using tritiated thymidine as described in numerous articles in the scientific literature.

See, e. g., Rey et al., Virology, 181 (1), 165-71,1991.

Results All results are based on RT analysis using tritiated thymidine, and are given in counts per minute (CPM).

Culture Series A, the control, demonstrated no viral replication in any cultures.

Culture Series B (without serum; Fig. 1A) demonstrated a significant reduction of viral replication in most cultures from vaccinated subjects when compared to unvaccinated subjects. Two subjects (1 and 10) showed a complete lack of viral replication, comparable to the controls in culture series A. One subject was excluded from all analyses when it was subsequently discovered that the subject had had a highly anomalous reaction to the vaccinia immunization with recurrent skin lesions for months afterward. This suggested an inadequate immune response to the vaccinia, and this subject correspondingly did not show any protection against HIV in cell culture, demonstrating viral replication comparable to unvaccinated subjects.

Culture Series C (with serum; Fig. 1B) also demonstrated a significant reduction of viral replication in most cultures from vaccinated subjects, when compared to unvaccinated subjects. The same two subjects (1 and 10) noted in culture series B also had no demonstrable viral replication, comparable to the controls in culture series A. The addition of autologous serum in culture series C further enhanced the difference between vaccinated and unvaccinated subjects when compared to culture series B (no serum).

Culture Series D, E and F, using the T-cell (CXCR4) tropic HIV (Fig. 1C), demonstrated no difference between vaccinated and unvaccinated subjects, including

the two subjects (1 and 10) who were resistant to infection by the macrophage (CCR5) tropic HIV in culture series B and C. As stated in the methods section, care was taken in the selection of subjects to avoid those of northern European descent who might be homozygous for the CCR5-delta32 mutation, so this cannot be an explanation for the described resistance. There was also no difference noted between the addition of serum and no serum (cultures D and E).

Discussion By at least day 10, there is a statistically significant difference between the vaccinated and non-vaccinated subjects in culture series B and C (p=. 035 and. 013 respectively) that increases by day 13 (p=. 017 and. 008 respectively), indicating a resistance to infection by HIV in the vaccinated subjects (Fig. 1). Subjects 1 and 10 demonstrated total resistance to macrophage (CCR5) tropic HIV infection in both culture series B and C, with RT measurements equal to the non-HIV infected control (culture series A). The fact that the same result was achieved in both sets of cultures, while infection was easily achieved with the T-cell (CXCR4) tropic HIV in cultures D, E and F, indicate these finding were not the result of laboratory error.

Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. The entire disclosure of all applications, patents and publications, cited above and in the figures are hereby incorporated by reference in their entirety, including of U. S. Provisional Application Nos. 60/491,258 filed July 31,2003, 60/493,767 filed August 11,2003, 60/496,908 filed August 22,2003, and 60/501,832 filed September 11,2003.

TABLE 1 THE OPEN READING FRAMES OF VACCINIA VIRUS Translation Size Genea Start Stop'References aa K rc Characteristxcs C23L* 5008 4277 244 26. 4 Nonessential ; B29R Perkus, et al. (1990b) Acidice (4. 2) C22L* 6113 5748 122 13. 6 Nonessential ; B28R Perkus, et al. (1990b) Hydrophobic N-terminus C21L* 6815 6477 113 13. 4 Nonessential ; B27R Perkus, et al. (1990b) C20L* 7132 6824 103 12. 5 Nonessential ; B26R Perkus, et al. (199Ob) Basic (9. 0) C19L* 7856 7080 259 30. 5 Nonessential ; B25R Perkus, et al. (1990b) Hydrophobic N-terminus C18L* 8693 8244 150 17. 5 Nonessential ; B24R Perkus, et al. (1990b) Acidic (4. 8) C17L* 9947 8790 386 44. 9 Nonessential ; B23R Perkus, et al. (1990b) C16L* 10539 9997 181 21. 0 Nonessential ; B22R Perkus, et al. (1990b) C15L*'11153 10881 91 10. 5 Nonessential ; B21R Perkus, et al. (1990b) C14L. 12212 11967 82 9. 3 Nonessential Perkus, et aZ. (1990b) Basic (9. 2) C13L 12510 12316 65 7. 4 Nonessential Perkus, et al. (1990b) Acidic (4. 0) C12L 13733 12675 353 40. 4 Serine Protease Inhibitor Kotwal and Moss (1988b) Nonessential Perkus, et al. (1990b) Acidic (4. 8) C11R 14178 14603 142 15. 8 Growth Factor Blomquist, et al. (1984) ; Brown, et al. (1985) ; Reisner (1985) Nonessential Buller, et al. (1988) ; Perkus, et al. (1990b) EGF-like type A domain Hydrophobic C-terminus C10L 15754 14762 331 38. 5 Nonessential Perkus, et al. (1990b) Acidic (4. 5) C9L 18136 16235 634 74. 7 Nonessential Peekus, et al. (1990b) ; Kotwal and Moss (1988b) C8L 18733 18182 184 21. 6 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) Acidic (4. 4) C7L 19257 18808 150 18. 0 Nonessential Kotwal and Moss (1988b) ; Perkus, et al . (1990a, b) Host range function Perkus, et al. (1990a) C6L 19939 19487 151 17. 4 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) Acidic (4. 8) C5L 20680 20069 204 24. 5 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) Acidic (4. 8)) C4L 21693 20746 316 37. 2 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) C3L 22551 21763 263 28. 6 Nonessential Kotwal and Moss (1988a, b) ; Perkus, et al. (1990b) C4B binding protein homolog ; virokine Kotwal and Moss (1988a) C2L 24156 22621 512 59. 2 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) Hydrophobic N-terminus C1L 24900 24229 224 26. 4 Nonessential Kotwal and Moss (1988b) ; Perkus, et al.. (1990b) Basic (9. 0) Reprinted from Virology, Vol. 179, S. J. Goebel, G. P. Johnson, M. E. Perkus, S. W. Davis, J. P. Winslow and E. Paoletti,"The Complete DNA-Sequence of Vaccinia Virus", pgs. 247-266 (1990), with permission from Elsevier.

TABLE 1-Continued Translation Size Gene Start stopb aa jf Characteristics References N1L 25240 24890 117 14. 0 Nonessential Kotwal and Moss (1988b) ; Perkus, et al. (1990b) Virokine Kotwal and Moss (1988a) Acidic (4. 2) N2L 25886 25362 175 20. 8 Nonessential Kotwal and Moss (1988a, b) ; Perkus, et al. (1990b) MIL 27346 25931 472 54. 2 Nonessential Perkus, et al. (1990b) Homology to K1L Perkus, et al. (1990a) M2L 27986 27327 220 25. 1 Nonessential Perkus, et al. (1990b) Hydrophobic N-terminus K1L 28975 28124 284 32. 6 Host range function Gillard, et al. (1986) ; Perkus, et al. (1989) Nonessential Perkus, et al. (1990b) K2L 30313 29207 369 42. 3 Serine protease inhibitor Boursnell, et al. (1988) Nonessential Perkus, et al. (1990b) Basic (9. 3) K3L 30629 30366 88 10. 5 Nonessential Perkus, et al. (1990b) Basic (9. 3) Translation initiation factor K4L 31955 30684 424 48. 9 Homology to F13L Boursnell, et al. (1988) Nonessential Perkus, et al. (1990b) K5L 32497 32090 136 15. 2 Nonessential Perkus, et al. (1990b) Basic (10. 2) K6L 32764 32522 81 9. 1 Nonessential Perkus, et al. (1990b) K7R 32903 33349 149 17. 5 Nonessential Perkus, et al. (1990b) Acidic (4. 4) Hydrophobic C-terminus F1L 34097 33420 226 26. 4 Nonessential Perkus, et al. (1990b) Acidic (4. 4) Hydrophobic C-terminus F2L 34552 34112 147 16. 3 Retroviral protease Slabaugh and Roseman (1989) Nonessential Perkus, et al. (1990b) dUTPase F3L 36018 34579 480 55. 7 Nonessential Perkus, et al. (1990b) F4L 36988 36032 319 37. 0 Ribonucleotide reductase Slabaugh, et al. (1988) (small subunit) Nonessential Perkus, et al. (1990b) Acidic (4. 6) F5L 37985 37023 321 36. 5 Multiply hydrophobic F6L 38239 38018 74 8. 6 Acidic (4. 1) F7L 38533 38258 92 11. 0- (Lys-Asn) g F8L 38878 38684 65 7. 8 Basic (9. 9) F9L 39576 38941 212 23. 8 Hydrophobic C-terminus F10L 40882 39566 439 52. 2 Protein kinase 2nd signature Fill. 41969 40908 354 39. 7- F12L 43919 42015 635 73. 2- F13L 45079 43964 372 41. 8 Envelope antigen Hirt, et al. (1986) F14L 45318 45100 73 8. 3 Acidic (2. 9) FISL 46068 45595 159 18. 6 Basic (9. 5) F16L 46770 46078 231 26. 6 Basic (9. 6) F17R 46833 47135 101 11. 3 Basic (9. 8) E1L 48574 47138 479 55. 6- E2L 50784 48574 737 85. 9- E3L 51483 50914 190 21. 5 Acidic (4. 9) E4L 52318 51542 259 29. 8 Acidic (4. 9) Transcription factor TABLE 1-Continued Translation Size Gene'3 Start Stopb aa Hrc Characteristics References (ts : C19? ?) f Condit, et al. (1983) E5R 52395 53387 331 39. 1 Basic (9. 8) E6R 53527 55227 567 66. 7 E7R 55314 55811 166 19. 5 E8R 55939 56757 273 31. 9 Basic (9. 3) E9L 59787 56770 1006 117. 0 DNA Polymerase Earl, et al., 1986 ts ; C42, NG26 ; PAAr, Aphidicolinr Traktman, et al. (1989b) DNA polymerase family B signature E1OR 59819 60103 95 10. 8- E11L 60490 60104 129 14. 9- OIL 62477 60480 666 77. 6 Leucine Zipper Motif 02L 62851 62528 108 12. 4 Glutaredoxin I1L 63935 63000 312 35. 8- I2L 64163 63945 73 8. 4 Hydrophobic C-terminus Acidic (3. 9) I3L 64973 64167 269 30. 0- I4L 67371 65059 771 87. 0 Ribonucleotide reductase Schmitt and Stunnenberg (1988) (large subunit) Tengelsen, et al. (1988) Nonessential Perkus, et al. (unpublished) Child, et al., (1990) Divalent Fe-S ferredoxin binding region signature I5L 67637 67401 79 8. 7 Basic (9. 9) I6L 68804 67659 382 43. 4 Basic (9. 2) I7L 70068. 68800 423 49. 0- I8R 70074 72101 676 77. 6 ATP/GTP binding motif A G1L 73883 72111 591 67. 9- G2R 74209 74868 220 25. 7- G3L 74215 73883 111 12. 8 Hydrophobic N-terminus G4L 75215 74844 124 14. 0 Acidic (4. 8) G5R 75218 76519 434 49. 9 Acidic (4. 8) G6R 76723 77217 165 18. 9- G7L 78300 77188 371 41. 9- G8R 78331 79110 260 29. 9- G9R 79133 80152 340 38. 8 Hydrophobic C-terminus L1R 80156 80905 250 27. 3 Hydrophobic near C-terminus L2R 80940 81200 87 10. 2- L3L 82245 81196 350 40. 6 Multiply hydrophobic L4R 82270 83022 251 28. 5 Structural protein, VP8 Yang, et al. (1988} L5R 83035 83418 128 14. 0 Basic (10. 0) J1R 83378 83836 153 17. 8- J2R 83855 84385 177 20. 1 Thymidine kinase Weir and Moss (1983) ; Hruby et al. (1983) Nonessential Mackett, et al. (1982) ATP/GTP binding motif A J3R 84454 85452 333 15. 2 Basic (10. 0) J4R 85370 85924 185 21. 3 RNA Polymerase subunit Broyles and Moss (1986) ts : C7, C20 Hooda-Dhingra, et al. (1989) ; Thompson, et al. (1989) J5L 86403 86005 133 15. 2 Hydrophobic C-terminus J6R 86510 90367 1286 146. 8 RNA Polymerase subunit Broyles and Moss (1986) ts : E8, E13, E72 Ensinger (1987) C51, C53, C65 Hooda-Dhingra, et al., (1989) ; Thompson, et TABLE 1-Continued Translation Size Genea Start Stopb aa Mrc Characteristics References H1L 90882 90370 171 19. 7 Basic (9. 6) H2R 90896 91462 189 21. 5 Hydrophobic N-terminus H3L 92442 91471 324 37. 5 Multiply hydrophobic H4L 94830 92446 795 93. 6- H5R 95016 95624 203 22. 3- H6R 95628 96569 314 36. 7 Basic (10. 0) DNA topoisomerase Shuman and Moss (1987) H7R 96609 97046 146 16. 9 D1R 97093 99624 844 96. 7 mRNA capping enzyme Morgan, et al. (1984) (small subunit) D2L 100026 99589 146 16. 9 ts : E52, E94 Seto, et al. (1987) D3R 100019 100729 237 28. 0 ts : C5, C35 Seto, et al. (1987) D4R 100732 101385 218 25. 0- D5R 101420 103774 785 90. 0 ts : C17, C24, E69 Seto, et al. (1987) ATP/GTP binding motif A D6R 103818 105728 637 73. 8 Early transcription Broyles and Fesler (1990) factor subunit ts : C46, E93 Seto, et al. (1987) Hydrophobic N-terminus D7R 105758 106240 161 17. 9 RNA polymerase subunit Ahn, et al. (1990) ts : C21, E45 Seto, et al. (1987) Acidic (4. 5) D8L 107120. 106209 304 35. 3 Carbonic anhydrase Niles, et al. (1986) Transmembrane Niles and Seto (1988) Cell surface binding Maa, et al (1990) Multiply hydrophobic Basic (9. 1) D9R 107162 107800 213 25. 0- D10R 107800 108543 248 28. 9- D11L 110442 108550 631 72. 4 NTPase Rodriguez, et al. (1986) ; Broyles and Moss (1987) ts : C36, C50, E17 Seto, et al. (1987) Basic (9. 0) D12L 111340 110480 287 33. 4 mRNA capping enzyme Niles, et al. (1989) (small subunit) D13L 113026 111374 551 61. 9 ts : C33, C43, E101 Seto, et al. (1987) Rifampicin resistance Tartaglia and Paoletti (1985) ; Baldick and Moss (1987) Acidic (5. 0) AIL'113502 113053 150 17. 0- A2L 114197 113526 224 26. 3 A3L 116372 114441 644 72. 6 Major core protein P4b Rosel and Moss (1985) A4L 117270 116428 281 30. 8 Acidic (4. 6) A5R 117308 117799 164 19. 0 Acidic (4. 2) A6L 118917 117802 372 43. 1- A7L 121073 118944 710 82. 3 Early transcription Gershon and Moss (1990) factor subunit A8R 121127 121990 288 33. 6- A9L 122285 121989 99 11. 1- A1OL 124961 122289 891 102. 3 Major core protein P4a Van Meir and Wittek (1988) A11R 124976 125929 318 36. 1 Hydrophobic C-terminus Acidic (4. 7) A12L 126512 125937 192 20. 5 Basic (10. 1) A13L 126748 126539 70 7. 7 Basic (9. 7) A14L 127128 126859 90 10. 0- A15L 127580 127299 94 11. 0- A16L 128700 127567 378 43. 6 Hydrophobic C-terminus A17L 129314 128706 203 23. 0 Hydrophobic center Acidic (4. 1) A18R 129329 130807 493 56. 7 Basic (9. 3) TABLE 1-Continued Translation Size Genea Start Stopb aa MrC Characteristics References A19L 131024 130794 77 8. 3- A20R 131377 132654 426 49. 2- A21L 131378 131028 117 13. 6 Hydrophobic N-terminus A22R 132620 133147 176 20. 7 Basic (9. 9) A23R 133170 134315 382 44. 6- A24R 134315 137806 1164 133. 4 RNA polymerase subunit ; Hooda-Dhingra, et al. (1990) ts : C27, C29, C32, C47, C62 Hooda-Dhingra, et al, (1990) Leucine Zipper Pattern A25L 138011 137817 65 7. 5 A-type inclusion protein Funahashi, et al. (1988) ; (cowpox virus) Acidic (3. 3) A26L 138948 137983 322 37. 3 A-type Inclusion protein Funahashi, et al. (1988) ; (cowpox virus) Basic (9. 2) A27L 139330 139001 110 12. 6 Fusion protein Rodriguez & Esteban (1987) A28L 139771 139334 146 16. 3 A29L 140689 139775 305 35. 4- A30L 140885 140655 77 8. 7 Basic (9. 9) A31R 141045 141416 124 14. 2 Basic (9. 0) Ribonucleoprotein RNA-binding region signature A32L 142288 141389 300 34. 4 Basic (9. 2) ATP/GTP Binding motif A A33R 142316 142870 185 20. 5- A34R 142897 143400 168 19. 5 Basic (10. 1) A35R 143447 143974 176 20. 0 Acidic (4. 0) A36R 144044 144706 221 25. 1 Acidic (4. 4) A37R 144773 145561 263 29. 9- A38L 146678 145848 277 31. 6 Multiply hydrophobic A39R 146695 147903 403 45. 7- A40R 147932 148435 168 19. 3 Hydrophobic N-terminus A41L 149155 148499 219 25. 1 Acidic (4. 8) A42R 149334 149732 133 15. 0 Basic (9. 9) Profilin A43R 149773 150354 194 22. 6- A44L 151733 150696 346 39. 4 3ß-Nydroxy-5-ene steroid dehydrogenase A45R 151780 152154 125 13. 8 Superoxide dismutase A46R 152147 152788 214 24. 7- A47L 153690 152959 244 28. 3 Basic (10. 0) A48R 153789 154400 204 23. 2 Thymidylate kinase Smith, et al. (1989a) ATP/GTP binding motif A Acidic (5. 0) A49R 154451 154936 162 18. 8 Acidic (3. 9) A50R 154972 156627 552 63. 4 DNA Ligase Colinas, et al. (1990) ; Smith, et al. (1989a) ; Rerr and Smith (1989) Nonessential Colinas, et al. (1990) A51R 156683 157684 334 37. 7 Nonessential Davis, et al. (unpublished) A52R 157757 158326 190 22. 7 Hydrophilic N-terminus AS3R 158635 158943 103 12. 0 Nonessential Davis, et al. (unpublished) A54L 158743 158474 90 10. 8 Basic (10. 4) Nonessential Davis, et al. (unpublished) A55R 159442 161133 564 64. 7 Nonessential Davis, et al. (unpublished) A56R 161186 162130 315 34. 8 Nonessential Shida, et al. (1987) Hemagglutinin Shida (1986) Hydrophobic C-terminus Acidic (3. 9) A57R 162278 162730 151 17. 4- TABLE 1-Continued Translation Size Genea Start Stopb aa M c Characteristics References SIR 162884 163783 300 34. 3 ts : C2, C3, C25 Traktman, et al. (1989a) Protein Kinase Howard and Smith (1989) Basic (9. 1) B2R 163876 164532 219 24. 6- B3R 164571 164942 124 14. 4 Acidic (4. 7) B4R 165603 167276 558 65. 3- B5R 167383 168333 317 35. 1 Multiply hydrophobic Acidic (4. 4) Complement control proteins C3L homologue B6R 168432 168950 173 20. 1- B7R 168991 169536 182 21. 3 Hydrophobic N-terminus B8R 169594 170409 272 31. 2 Hydrophobic N-terminus B9R 170499 170729 77 8. 8- B10R 170695 171192 166 18. 9- B11R 171267 171530 88 9. 9 Acidic (3. 6) M (DT) DVTNV B12R 171600 172448 283 33. 4 Protein Kinase Howard and Smith (1989) B13R 172562 172909 116 12. 8 Hemorrhage-inducing Pickup, et al. (1986) Serine Protease Inhibitor Kotwal and Moss (1989) ; Nonessential Perkus, et al. (1990b) Acidic (4. 6) B14R 172887 173552 222 24. 9 Hemorrhage-inducing Pickup, et al. (1986) Serine Protease Inhibitor Kotwal and Moss (1989) Nonessential Perkus, et al. (1990b) Acidic (4. 3) 215R 173632 174078 149 17. 4 Nonessential Perkus, et al. (1990b) Acidic (4. 5) B16R 174272 175141 290 32. 5 Nonessential Perkus, et al. (1990b) Kinase-related transforming protein B17L 176212 175193 340 39. 5 Nonessential Perkus, et al. (1990b) B18R 176349 178070 574 68. 1 Nonessential Perkus, et al. (1990b) B19R 178145 179203 353 40. 9 Hydrophobic N-terminus Nonessential Perkus, et al. (1990b) B20R 179300 179680 127 15. 5 Nonessential Perkus, et al. (1990b) Acidic (4. 1) B21R* 180585 180857 91 10. 5 Nonessential ; C15L Perkus, et al. (1990b) B22R* 181199 181741 181 21. 0 Nonessential ; C16L Perkus, et al. (1990b) B23R* 181791 182948 386 44. 9 Nonessential ; C17L Perkus, et al. (1990b) B24R* 183045 183494 150 17. 5 Nonessential ; C18L Perkus, et al. (1990b) Acidic (4. 8) B25R* 183882 la4658 259 30. 5 Hydrophobic N-terminus Nonessential ; C19L Perkus, et al. (1990b) B26R* 184606 184914 103 12. 5 Nonessential ; C20L Perkus, et al. (1990b) Basic (9. 0) B27R* 184923 185261 113 13. 4 Nonessential ; C21L Perkus, et al. (1990b) B28R* 185625 185990 122 13. 6 Nonessential ; C22L Perkus, et al. (1990b) Hydrophobic N-terminus B29R* 186730 187461 244 26. 4 Nonessential ; C23L Perkus, et al. (1990b) Acidic (4. 2) 'Open reading frames enumerated as described in text. b Translation stop does not incude the three bases of termination codon.

° M, values calculated for the nascent, unprocessed polypeptide chain are presented as kDa.

"Functions or activities indicated in bold type are known functions of vaccinia virus. Those indicated in italic have been identified in this study on the basis of similarity to existing proteins. All others are possible functions previously described by other investigators.

° Acidic proteins: p/< 5.0 ; basic proteins: pl > 9.0. p/presented within parentheses.

'Temperature-sensitive mutants indicated by ts. Those first isolated by Condit et al. (1983) are prefaced with C ; 1 begin with E. Mutant C19, while not localized to a particular open reading frame, appears to map in the vicinity of I * Open reading frames repeated in both left and right termini of genome.

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TABLE2 Features and Homologies of Open Reading Frames of the Vaccinia MVA Strain ORF'START AA° kDu name/ (putattve) BLAST° BLAST° HSS'references STOPfunction/homoiOEies"expect AAid (%) left terminal region : 001L/õ822 136 14. 9 35k major seer. protein (Pateì ez z1. \990) 193Rh 6412 chemokine receptor (f) (Graham er al., 1997) C23L 244 VAC (C23L/B29R) 6. 0e-57 41/42 97 (Goebel et al., 1990) 253 VAR-1'G3R 8. 9e-51 46/49 93 (Shchelkunov et al., 1995) 246 CPXORFB 5. 6e-49 40/42 95 (Hu et aL"1994) 258 SFV Tl protein 2. 5e-20 23/42 54 (Uptoa et caL 1987) 260 Myxoma virus Tl/35kDa 1. 5e-14 21142 50 (Graham et al., 1997) 002L/7784 176 19. 7 secr. TNF receptor (f) (Upton et al., 1991a) 192R"7254 355 CPXcrmB 5. 1e-71 76/83 91 (Hu etal., 1994) 348 VAR-BSH G2R l. Oe-66 73/83 87 (Shchelkunov et al. 1995) 326 Myxoma virus T2 4. 9e-30 21/37 56 (Upton rt al., 1991a) 325 Rabbit fibroma Virus T2 1. 8e-28 17/36 47 (Upton et al., 1987) 202 CPXC4L 8. 7e-15 30/51 58 (Safronov et cil., 1996) 3446'HS TNF receptor protein 1. 9e-OS 14126 53 (Heller er al., 1990) C19L 259 VAC (Cl9L/B25R) 0. 00026 16119 84 (Goebel et Ill. 1990) 277 human CD40L receptor 0. 0015 l l/24 45 (Statnencovic et al 1989) 30 matches to TNF receptors <0. 39 and surface proteins 003L/8780 102 12. 1 45k ankl-like protein (Goebel et al., 1990) 191R"8472 (fl) Cl 7L 386 VAC C17L./B23R 1. 3e-39 62163 98 (Goebel et at., 990) 004L/9558 233 26. 9 45k ank-like protein (Goebel et al. 1990) 190R'8857 (f2) C17L 386 VAC (C17LIB23R) 6. 2e-159 1101110 100 (Goebel et al., 1990) DIL 91 VAR-BSH 9. 1 e-31 46/49 93 (Shchelkunov et al., 1995) 669 CPX host range l. le-13 22150 44 (Spehner et al., 1988) 452 VAR-) D6L (BSH : D8L) 1. 7e-11 21150 42 (Shchelkunov et al., 1995) 574 VAR-I B19R (BSH : B16R) 1. 2e-05 22/73 30 (Shchelkunov et al. 1995) 574 VAC B18R (WR : B17R) 8. 6e-05 22/73 30 (Goebel et al., 1990j 634 VACC9L 0. 00011 11/24 45 (Kotwal and Moss 1988a) 585 VAR-1 GIR 0. 00013 22/74 29 (Shchelkunov et al., 1995) 516 orf virus 0. 0088 15/49 30 (Sullivan et al., 1995b) 153 VAR-1 D71. (BSH : DIOL) 0. 014 12/28 42 (Shchelkunov et al., 1995) OOSR 10203 140 15. 5 Growth factor (EGF (Twardzik et al., 1985) 10625 receptor binding) (Stroobant et al., 1985) CIIR 142 VAC 2. 9e-82 991104 95 (Goebel et a/., 1990) D2R 140 VAR-1 (BSH : 04R) 3. 6e-74 106/140 75 (Shchelkunov et al., 1995) 138 CPXDSR 3. 4e-95 101/114 88 (Safroitov et til., 1996) 169 human epiregulin 2. 2e-14 29178 37 D30783 100 matches to growth factor <0. 10 like sequences 006L 11758 326 37. 9 37. 9k protein (Venkatesan et al., 1982) CIOL 10778 331 VAC 1. 7e-235 2641268 98 (Goebel et al., 1990) 331 CPXD6L 7. 7e-235 2641268 98 (Safronov er al., 1996) D5L 330 VAR-BSH (1 : D3L) 3. 6e-233 169/171 97 (Shchelkunov et al., 1995) 3l6 VAR-1 Dl IL (BSH : D14L) 1. 7e-94 34/68 44 (Shchelkunov et al., 1995) 316 VACC4L 1. 8e-92 30/68 54 (Goebel et al., 1990) 315 CPXD16L 2. 3e-92 31/68 45 (Safronov et zzl. 1996) 82 Ectromelia 42K protein 1. 2e-50 78/82 95 (Senkevich et al., 1993a) 418 FPV BamHl ORFI 3. 0e-11 13/41 31 lTomleY et al., 1988) 007R 12263 91 10. 6 28k virulence factor (f) (Senkevich et aL, 1993a) 12538 242 CPXD7R 1. 5e-51 42/47 89 (Safronov et al., 1996) 184 VAC-WR 21. 7k protein 5. 3e-51 41/47 87 (Kotwal and Moss, 1988a) D4R 242 VAR-) (BSH : D6R) 3. 7e-50 41/47 87 (Shchelkunov et al., 1995) 241 Ectromelia 28k secreted 3. 7e-50 41/47 87 (Senkevich etc al., 1993a) virulence factor 008L 13414 120 13. 7 13. 7k protein D7L 13052 126 VAR-BSH () : D5L) 1. 9e-83 57/64 89 (Shchelkunov er al., L995) 138 Ectromelia 16k protein 7. 8e-81 58160 96 (Senkevich et al., 1993a) 124 CPXD8L 3. 2e-67 49/60 81 (Safronov et al., 1996) 68 7. 8k protein (VAC-WR) 1. 3e-34 53/64 82 (Kotwal and Moss, 1988a) 009L 13745 90 10. 7 77k CPX hr protein (fl) (Spehner er al., 1988) 13473 669 CPX host range gene 2. 7e-46 43/52 82 (Safronov et al"1996) 634 VACC9L 1. 7e-05 9133 27 (Goebel rt al., 1990) 010L 14186 142 16. 1 77k CPX hr protein (f2) (Spehner et al., 1988) 13758 669 CPX host range gene 2. 2e-91 133/142 93 (Safronov er al., 1996) 634 VACC9L 9. 2e-21 26/63 41 (Goebel et al., 1990) D6L 452 VAR-I (BSH : D8L) 4. 5e-13 27/29 93 (Shchelkunov et al 1995) ) 50 VACCt8UB24R). 3e-)) 19/52 36 (Goebel et a/., 1990) 439 AT ankyrin repeat protein 9. 5e-07 23159 38 (Zhang et al., 1992) 558 VAR-t B6R (BSH : B5R) 4. 0e-05 281113 24 (Shchelkunov et al., 1995) 30 matches with ankyrin 2. 7e-05 to repeat containing proteins 0. 016 011L 14682 135 15. 8 77k CPX hr protein (f3) (Spehner et al., 1988). 14275 669 CPX host range gene 7. 6e-80 54/64 84 (Safronov et al. 1996) D6L 452 VAR-I (BSH : D8L) 9. 2e-78 52164 81 (Shchelkunov et al. 1995) 012L 15183 90 10. 3 77k CPX hr protein (f4) (Spehner et al.. 1988) Reprinted from Virology, Vol. 244, G. Antoine, F. Scheiflinger, F. Dorner, and F. G.

Falkner, "The Complete Genomic Sequence of the Modified Vaccinia Ankara Strain: Comparison with Other Orthopoxviruses", pgs. 365-396, (1998), with permission from Elsevier.

GENOMIC SEQUENCE OF THE MVA STRAIN ORF'START AA"kDu name/ (putative) BLAST'BLAST'HSS'references STOP function/homologiest expect AA id (%) left terminal region : iML h491) 452 VAR-I (BSH : D8L) 2. 2e-52 80/85 94 (Shchelkunov er al., 1995) 669 CPX host range gene 8. 1e-51 77/85 90 (Spehner et al. 1988) 153 VAR-I D7L (BSH : DIOL) 2. 9e-17 19/45 42 (Shchelkunov et al., 1995) 634 VACC9L 1. 3e-13 19/45 42 (Goebel et al. 1990) 1161 C. botulinum NTNH protein 0. 00019 6/12 50 (Hutson et aL, 1996) 202 Capripox 0. 00058 15/58 25 (Cao et al., 1995) 895 UDP glucose dehydrogenase 0. 00051 6/19 31 (Bult et al. 1996) 516 orf virus ank-like 0. 0064 16/49 32 (Sullivan et al., 1995b) 673 rabbit fibroma 77. 2k protein 0. 0072 12/30 40 (Massung ei al 1992) 013L 15420 71 8. 5 77k CPX hr protein (fS) (Spehner ex al., 1988) 15205 669 CPX host range gene 5. 2e-44 68/69 98 (Safronov et au 1996) D6L 452 VAR (BSH : D8L) 7. 9e-42 64167 95 (Shchelkunov et al 1995) 673 rabbit fibroma 77. 2k protein 0. 0052 8/26 30 (Massung et al., 1992) 386 VAC C17UB23R 0. 018 14/33 42 (Goebel et al. 1990) 202 Capripox 0. 023 10/19 52 (Sullivan et al., 1995b) 574 VAC B18R (WR : B17R) 0. 71 12/28 42 (Goebel et al. 1990) 574 VAR B19R (BSH : B16R) 0. 71 12/28 42 (Shchelkunov ei al. 1995) 014L 16205 109 13. 1 75k ank-like gene (fl) (Kotwal and Moss, 1988a) C9L 15876 634 VAC 3. 9e-73 109/109 100 (Goebel et al. 1990) 614 CPXDIIL 1. 6e-70 105/108 97 (Safronov et aL 1996) D9L 91 VAR (1 : D6. 5L) 1. 2e-52 78/91 85 (Shchelkunov et al., 1995) 437 CPXD1L 3. 7e-19 28/67 41 (Safronov et al. 1996) 673 rabbit fibroma 77. 2K protein 0021 5/16 31 (Massung et al. 1992) O15L 16786 96 11. 2 75k ank-like gene (f2) (Kotwal and Moss 1988a) C9L 16496 634 VAC 4. 0e-53 80/80 100 (Goebel et aL 1990) 614 CPXDIIL 3. 9e-25 48/80 60 (Safronov et al., 1996) 437 CPXDIL 9. 6e-12 14/36 38 (Safronov et al. 1996) 172 VAR-Garcia 1966 BIIL 0. 0001 17/17 100 (Massung et al., 1996) 141 integrase (simian foamy v.) 0. 033 10/24 41 (Schweizer and Neumann, 1995) 669 CPX host range gene 0. 043 9/17 52 (Spehner et al., 1988) 016L 17759 297 35. 0 75k ank-like gene (f3) (Kotwal and Moss, 1988a) C9L 16866 634 VAC 3. 4e-208 291/294 98 (Goebel et al., 1990) 614 CPXDIIL 1. 4e-130 90/126 71 (Safronov et at., 1996) D7L 153 VAR-1 (BSH : DIOL) 8. 4e-68 84/109 77 (Shchelkunov et al., 1995) 669 CPX host range gene 4. 5e-17 24/61 39 (Spehner et at., 1988) 452 CPXD9L 2 2e-16 23/61 37 (Safronov et aL, 1996) D8L 668 VAR-BSH (I : D6L) 3. 3e-16 21/61 34 (Shchelkunov et al., 1995) 386 VACC17L/B23R 2. 9c-OS l l/24 45 (Goebel er al., 1990) 833 CPXD3L 0. 0085 13/58 22 (Safronov et al., 1996) 574 VAC BIER (WR : B17R) 0. 012 13/40 32 (Goebel et al. 1990) 202 Capripox virus 0. 084 l l/29 37 (Sullivan er al. 1995b) 574 VAR-I B19R (BSH : B16R) 0. 090 13/40 32 (Shchelkunov et al., 1995) 017L 18335 177 20. 8 20. 8k protein (Kotwal and Moss, 1988a) C8L 17802 184 VAC 1. 2e-125 125/129 96 (Goebei et aL 1990) 182 CPXD12L 5. 0e-H8) 19/126 94 (Safronov et al., 1996) 182 VAC B7R 8. 3e-06 16/67 23 (Goebel et al., 1990) 795 VAC H4L (RAP94) 0. 60 12/45 26 (Goebel er al. 1990) 018L 18859 150 18. 0 host range protein (Perkus et al., 1991) C7L 18407 150 VAC 1. 6e-106 150/150 100 (Kotwal and Moss. 1988a) DIIL 150 VAR-BSH (I : D8L) 4. 2e-106 149/150 99 (Shchelkunov et al., 1995) 185 Swinepox virus ORF SwF8a 3. 4e-35 31/82 37 (Schnitzlein and Tripathy, 1991) 197 Capripox virus ORF CF8a 1. 4e-31 29/87 33 (Gershon and Black, 1989a) 170 CPXD4L 3. 5e-17 19/60 31 (Safronov et al.. 1996) 158 Myxoma virus ORF MF8 5. 6e-13 16/43 37 (Jackson and Bults, 1992) 128 VAR-BSH D3L (I : DI. 5L) 5. 4e-06 18/60 30 (Shchelkunov et al., 1995) 019L 19541 157 18. 2 18. 2k protein (Kotwal and Moss 1988a) C6L 19068 151 VAC 7. 6e-104 L511151 100 (Goebel et al., 1990) D9L 156 VAR (BSH : D12L) 1. 6e-99 145/150 96 (Shchelkunov et aL 1995) 156 CPXD14L 1. 3c-96 141/150 94 (Safronov et al. 1996) 159 Capripox virus ORF T3a 4. 4e-07 24/76 31 (Gershon and Black, 1989a) 151 Rabbit fibroma virus T3Aa 0. 0047 16/46 34 (Upton et al., 1987) 181 VACC16L/B22R 0. 2 12/46 26 (Goebel e ! al. 1990) 149 VARC4R 0. 29 8/13 61 (Shchelkunov er al., 1995) 149 VAC-WR K7R 0. 40 8/13 61 (Kotwal and Moss, 1988a) 020L 20025 113 13. 2 14k virulence factor, (Kotwal and Moss, 1988a) 19684 secreted protein (f) (Kotwal and Moss, 1988b) Nit 117 VAC 2. 6e-60 92/102 90 (Goebel er aL 1990) 117 CPX PIL 7. 3e-58 85/102 83 (Shchelkunov et aL 1995) P1L 117 VAR-BSH, virokine 6. 6e-56 88/102 86 (Safronov et al., 1996) 107 Rabbit fibroma virus 0. 015 10/17 58 (Massung et al., 1992) 021L 20656 170 20. 3 alpha-amanitin sensitive (Tamin et al., 1991) 20144 protein (Kotwal and Moss. 1988a) 175 CPXP2L 3. 0e-118 138/142 97 (Safronov et al., 1996) N2L 175 VAC 6. 1e-118 137/142 96 (Goebel el aL, 1990) P2L 177 VAR 9. 7e- 115 135/142 95 (Shchelktinov et al., 1995) 022L 20981 98 11. 0 33k host range gene (f) (Gillard et al., 1986) KIL 20685 284 VAC 1. 8e-56 86/88 97 (Aitenburger er al., 1989) 284 CPXM1L 2. 3e-56 86/88 97 (Safronov et al., 1996) CIL 66 VAR 2. 0e-39 63/66 95 (Shchelkunov et al., 1995) 65 human NOTCH 2 0. 00036 17/41 41 (Katsanis er al"1996) ORF'START AA'kDa'name/ (putative) BLAST° BLAST HSS'references STOP function/homologies"expect AA id f%) left terminal region : 023L 22296 369 42. 3 serpin SPI-3, cell-cell (Boursnell et au. 1988) 21187 fusion mutation (Altenburger et ai., 1989) K2L 369 VAC 1. 2e-258 365/369 98 (Goebel et al., 1990)] C2L 373 CPX M2L 1. 2e-250 331/337 (Safronov et aL 1996) 373 VAR-BSH 9. 9e-249 321/337 95 (Shcllelkunov et al., 1995) 373 Ectromelia virus H14-B 6. 5e-244 312/337 U67964 386 HS plasminogen activator l. le-35 30/68 44 (Loskutoff et al. 1987) inhibitor I 58 CPX SPI 3 protein 82e-33 57158 98 gi : 1168082 369 Myxoma virus MAPI gene 7. 3e-32 33/131 25 (Upton et al., 1990a) 397 mouse protease nexin 1. 5e-29 31167 46 (Vassalli et aL 1993) 397 humane glia derived neurite-8. 7e-27 30/65 46 A03911 promoting factor 320 Swinepox SPI like protein 3. 6e-21 20/70 28 (Massung et al., 1993) 417 a-l antitrypsin human 2. 2e-20 26/66 39 (Ciliberto et al.. 1985) 383 Corticosteroid-binding 9. 0e-20 (Seralini et al 1989) protein (rabbit) 390 squamous cell carcinoma 1. 9e-17 (Schneider et al. 1995) antigen 024L 22612 88 10. 5 IFN resistance, e'F-2x (Beattie et al., 1991) 22346 homolog (Davies et al. 1992) 88 CPXM3L 2. 6e-61 88/88 100 (Safronov et al., 1996) K3L 88 VAC 1. 4e-60 87/88 98 (Goebel et aL ; 990) C3L 88 VAR-I 1. 0e-52 73/88 82 (Shchelkunov et al., 1995) 86 SPV C8 protein 4. 1e-22 20/44 45 (Massung et al. 1993) translation initiation factor 2 1. 2e-08/ family 0. 45 025L 23938 424 43. 9 phospholipase D-like (Cao et al.. I997) 22664 protein K4L 424 VAC 1. 5e-306 423/424 99 (Goebel et al., 1990) 424 CPXM4L 2. 1e-303 416/424 98 (Safronov et al. 1996) 437 human HU-K4 2. 8e-135 53/95 55 U60644 372 D. discoideum 2. 5e-91 28/47 59 (Giorda et al 1989) 516 C. elegans 6. 6e-89 31/61 50 gi : 2435624 2327 C. elegans 2. 8e-52 36/60 60 gi : 2291241 635 C. elegans l. le-24 19/53 35 (Wilson et al. 1994) 377 FPV major envelope protein 2. 9e-23 19/61 31 (Calvert et al. 1992) 371 Myxoma virus env protein 3. 6e-22 18/51 35 U43549 378 Orf virus env protein B2L 1. 2e-21 21/71 29 (Sullivan et al., 1994) MC021L 388 MCV subtype 1 env protein 3. 2e-21 20/63 31 (Senkevich et al 1997) C17L 372 VAR-BSH 4. 6e-19 15/52 28 (Shchelkunov et al., 1995) 372 VAC F13L 4. 9e-17 15/52 28 (Goebel et al., 1990) 026L 24478 170 19. 1 lysophospholipase-like (Upton & Buller, unpub.) 23966 protein (fl) 276 CPX M5L 2. 6e-110 161/170 94 (Safronov et al. 1996) 277 Ectromelia virus H14-E 2. 7e-109 160/170 94 X94355 U67964 K5L 136 VAC S. Se-69 107/108 99 (Goebel et al. 1990) 134 VAC-WR 8. 3e-63 98/tOt 97 (Boursnell et au 1988) 313 HS lysophospholipase 3. 3e-35 35/lO5 33 U67963 323 homolog 1. 2e-13 30/94 31 Z97050 poss. oxidoreductase M. 324 tuberculosum 3. 1e-5 13/58 22 U9S973 Lysophospholipase isolog 313 A. thaliana 0. 047 13/30 43 U32747 H. influenza probable lysophospholipase L2 027L 24694 64 7. 0 lysophospholipase-like (Upton & Buller unpub.) 24500 protein (f2) K6L 81 VAC 5. 3e-42 63/63 100 (Boursnell et al., 1988) 276 CPXMSL 2. 4e-36 57/58 98 (Safronov et al., 1996) 277 Ectromelia virus H14-E 2. 4c-36 57/58 98 U67964 313 HS lyophospholipase homolog 9. 1e-23 34/53 64 U67963 323 hyp. oxidoreductase M. 9. 9e-14 22/54 40 Z97050 tuberculosis 530 dihydrotestosterone/androsta 7. 0e-05 6/17 35 A48633 nedlol UDP-glucuronosyl- transferase central conserved region : 028R 24864 149 17. 5 17. 5k protein (Goebel er al., 1990) K7R 25313 149 VAC 6. 1e-105 1492149 100 (Goebel e 1. 1990) 161 CPXM6R 1. 6e-101 144/149 96 (Safronov et al. 1996) C4R 149 VAR 4. 9e-lOl 143/149 100 (Shchelkunov et ai., 1995) 236 Swinepox (sc76) 0. 00017 19/49 95 (Massung et al. 1993) 029L 26046 222 25. 9 25. 9k protein (Roseman and Slabaugh, 1990) FIL 25378 226 VAC 2. 7e-158 208/211 98 (Goebel et at., 1990) 238 CPXGIL 7. 0e-148 166/189 87 (Safronov er al. 1996) CSL 2SI VAR-I 6. 6e-147 184/200 92 (Shchelkunov et al. 1995) 030L 26501 147 16. 2 dUTPase (Roseman and Slabaugh, 1990) 26058 (Roseman ea aL 1996) F2L 147 VAC 2. 9e-102 147/147 100 (Goebel et at., 1990) 147 CPXG2L 8. 2e-100 144/147 97 (SaFronov er al. 1996) C6L 147 VAR I. le-97 142/147 96 (Shchelkunov et al. 1995) 164 human dUTPase 4. 1e-61 49/69 71 (Ladner et al., 1996) ORF START AAb kDa name/ (putative) BLASTd BLAST XISSr referenees STOP fllnction/homologless expect AA id (%) left terminal region : -142 Swinepox virus 8. 0e-56 43/70 61 (Massung et al.-1993) 159 orf virus 1. Se-49 45/69 65 (Mercer et at., t989) 178 avian adenovirus 6. 6e-49 40/70 57 (Akopian et al., 1992) 1124 FIV poi polyprotein 1. 5e-26 49/117'41 (Talbott et al., 1989) dUTPase pyrophosphatuse >4. 2e-06 family 031L 27955 476 55. 3 kelch-like protein (Senkevich et al., 1993b) 26525 (Roseman and Slabaugh, 1990) F3L 480 VAC 0. 0 292/294 99 (Goebel et al., 1990) 485 CPXG3L 0. 0 287/293 97 (Safronov et al., 1996) C7L 179 VAR- 1. 9e-124 166/179 92 (Shchelkunov et aL, 1995) 500 Swinepox virus protein C13 4. 4e-46 39/133 29 (Massung et al., 1993) 564 VAC A55R 2. 8e-21 17/51 33 (Goebel et al., 1990) 689 kelch protein D. melanogaster 5. 3e-18 21/65 32 (Xue and Cooley, 1993) 512 CPXD18L i. 4e-16 15/33 45 (Safronov et aL, 1996j 512 VAC C2L 1. 6e-16 15/33 45 (Goebel et al., L990) 625 T27E9. 4 C. elegans 3. 7e-t4 15/59 25 Z82059 624 human KIAAOt32 protein 1. 9e-13 13/60 21 D50922 o. k 817 R09A8. 3 (C. elegans) l. le-12 17145 37 (Wilson et al., 1994) 611 C47D12. 7 (C. elegans) 2. 4e-12 22/91 24 (Wilson et al., 1994) 530 Swinepox virus 3. 0e-09 14/58 24 (Massung et al., 1993) 589 MM'"actin binding protein l. 9e-09 18/88 20 U65079 521 CPXCL 1. 2e-08 15/37 40 (Safronov et al., 1996) 509 Myxoma virus MT-9 2. 5e-08 17/58 29 (Upton et al., 1990a) 202 Murine lAP-promoted 4. 3e-08 17156 30 (Chang-Yeh et al., 1991) placenta (MIPP) expressed 326 protein 3. 9e-06 22/80 27 Z99708 559 A. thaliana hyp. protein 9. 0e-6 12/31 38 (Senkevich et al., 1993b) 916 Ectromelia virus p65 0. 00016 13/42 30 (Way et al., 1995) 172 B-scruin (L. polyphemus) 0. 018 15/36 41 (Shchelkunov et al., 1995) VAR-I J8R (BSH : 16R) 032L 28925 319 37. 0 ribonucleotide reductase (Slabaugh et aL, 1988) 27966 (small subunit) (Rosemun and Slnbnugh, 1990) 319 CPXG4L 2. 3e-231 317/319 99 (Safronov et al., 1996) F4L 319 VAC 3. 5e-231 3171319 99 (Goebel et al., 1990) C8L 333 VAR-BSH 4. 1e-228 313/319 98 (Shchelkunov et al., 1995) ribonucleotide reductase >2. 2e- 10 family 033L 29250 97 !).) 36. 5k major membrane (Roseman and Slabaugh, 1990) 28957 protein precursor (fl) C9L 348 VAR-BSH 1. 9e-36 51/53 96 (Shchelkunov et al., 1995) 323 CPXG5L 2. 4e-19 47/77 61 (Safronov et al., 1996) F5L 321 VAC 3. 3e-19 42/70 60 (Goebel et al"1990) 1584 non-receptor tyrosin kinase 0. 00038 15/35 42 (Tan and Spudich, 1990) (Dictyostelium discoideum) 034L 29875 218 24 8 36. 5k major membrane (Roseman and Stabaugh, 1990) 29219 protein precursor (f2) 323 CPXG5L 8. 2e-155 215/217 99 (Safronov et al., 1996) F5L 321 VAC 6. 4e- 155 215/217 99 (Goebel el at., 1990) C9L 348 VAR-BSH 6. 8e-141 186/210 88 (Shchelkunov et al., 1995) 035L 30129 74 8. 6 8. 6k protein (Roseman and Slabaugh, 1990) F6L 29905 74 VAC 5. 5e-47 74/74 100 (Goebel et al., 1990) C10L 72 VAR 2. 3e-38 62/70 88 (Shchelkunov et al., 1995) 036L 30387 80 9. 4 9. 4k protein (Roseman and Slabaugh, 1990) CUL 30145 79 VAR 2. 9e-44 34/43 79 (Shchelkunov et al., 1995) F7L 92 VAC 1. 9e-43 65/65 100 (Goebel et al., 1990) 037L 30731 65 7. 9 7. 9k protein (Roseman and Slabaugh, 1990) F8L 30534 65 VAC 5. le-43 63/65 96 (Goebel et al., 1990), C12L 65 VAR-I 3. te-4) 61/65 93 (Shchelkunov et al., 1995) 038L 31429/212 23. 8 23. 8k protein (Roseman and Slabaugh, 1990) F9L 30791 212 VAC 7. 1e-148 212/212 100 (Goebel et al., 1990), C13L 212 VAR 1. 2e-144 207/212 97 (Shchelkunov et al., 1995) 215 Swinepox virus 8. 1e-72 39/93 41 (Massung et al., 1993) MC016L 213 MCV subtype 1 2. 8e-62 711152 46 (Senkevich et al., 1996) 225 Orf virus 5. 1e-39 27/84 32 (Mercer et al., 1995) 243 FPV protein FP2 2. 8e-17 26/58 44 (Binns er al., 1988) 243 MCV subtype I MC069R 7. 7e-12 23/58 39 (Senkevich et al., 1996) 250 VAC LIR l. le-07 20/58 34 (Goebel et al., 1990), 250 VAR MIR l. te-07 20/58 34 (Shcllelkunov et al"1995) 039L 32735 439 52. 1 scrine/threonlne protein (Lin and Broyles, 1994) 31416 kinase 2 (Wang and Shuman, 1995) FJOL 439 VAC 0. 0 429/439 97 (Goebel et al., 1990), C14L 439 VAR-BSH 0. 0 424/439 96 (Shchelkunov et al., 1995) 440 Swinepox virus 2. 2e-233 151/214 70 (Massung et al., 1993) MC017L 443 MCV subtype 1 2. 3e-198 178/282 63 (Senkevich et al., 1996) 498 orf virus 2. 2e-162 198/366 54 (Mercer et al., 1995) 040L 33012 84 9. 6 39. 7k protein (fl) Ct5L 32758 354 VAR 6. 6e-27 50/64 78 (Shcllelkullov et al., 1995) FLAIL 354 VAC 9. 1e-27 50/64 78 (Goebel et al., 1990) 041L 33771 100 11. 4 39. 7k protein (f2) ! ORF'START AA"kDa name/ (putative) BLAST° BLAST HSS'references STOP Eunetion/llolilologlesr expect AA id (%) left terminal region : IFIIL 133469 354 VAC 3. 8e-62 95/95 100 (Goebel et al., 1990). CISL 354 VAR 8. 8e-58 90/95 94 (Shchelkunov er al. t995) 042L 35721 635 73. 1 73. 1k protein FI2L 33814 635 VAC 0. 0 629/63599 (Goebe) « a/.. 1990), C16L 635 VAR-1 0. 0 607/63595 (Shcheikunov efai., 1995) 352 Myxoma virus 3. 6c-84 28166 42 U43549 MC019L 663 MCV subtype (4. oye-60 29/82 35 (Senkevich et al., 1996) 640 orf virus 4. 8e-39 19/61 31 U34774 630 FPV F12 homolog 2. 3e-15 19/67 28 (Ogawa et aL 1993) (Hirt ct al., 1986) 043L 36866 372 41. 8 37k major EEV antigen 35748 IMCBH sensitive protein (Schmutz et al., 1991) palmitylprotein (Grosenbach et al., 1997) F13L 372 VAC 2. 1e-268 369/372 99 (Goebel et al. 1990) C17L 372 VAR-BSH 8. 9e-265 364/372 97 (Shchelkunov er al. 1995) 371 Myxoma virus 2. 5e-115 110/200 55 U43549 378 orf virus 7. 6e-108 83/194 42 (Sullivan et al. 1994) MC021L 388 MCV subtype 1 6. 1e-98 44/113 38 (Senkevich et al. 1996) 377 FPV major env protein 2. 8e-88 47/112 41 (Calvert et al. t992) 251 pigeonpox virus I. 8e-62 47/112 41 S27933 424 CPXM4L 2. 1e-18 16/52 30 (Safronov et al., 1996) 424 VACK4L 1. 7e-17 14/35 40 (Goebel et al. 1990) 372 D. discoideum 1. 4e-16 28/84 33 (Giorda et al. 1989) 437 HU-K4 (homo sapins) 1. 5e-11 25/94 26 U60644 044L 37105 73 8. 3 8. 3k protein F14L 36884 73 VAC 2. 3e-44 72/73 98 (Goebel et al. 1990) C18L 73 VAR 2. ive35 57/73 78 (Shchelkunov et al. 1995) 045L 378533 158 18. 6 18. 6k protein F15L 37377 158 VAC 2. 3e-112 157/158 99 (Goebel et al. 1990) C19L 161 VAR 1. 4e-107 1501153 98 (Shchelkunov et al.. 1995) MC025L 148 MCV subtype 1 3. 5e-54 52/113 46 (Senkevich et al., 1996) 148 Myxoma virus 5. 4e-50 48/112 42 U43549 046L 38555 Mi 26. 5 26. 5k protein F16L 37860 231 VAC 3. 3e-159 2271231 98 (Goebel er at., 1990), C20L 231 VAR 5. 6e-157 222/231 96 (Shchelkunov et al. 1995) 209 Myxoma virus 8. 3e-48 26/58 44 U43549 MC029L 230 MCV subtype 1 6. 9c-45 16/61 26 (Senkevich et al., 1996) 047R 38619 101 11. 3 Ilk DNA binding (Bertholet et al., 1985) 38924 phosphoprotein (Kao and Bauer, 1987) F17R 101 VAC 3. 0e-69 100/101 99 (Goebel et al. 1990) C21R 101 VAR 9. 7e-67 99/101 98 (Shchelkunov et at., 1995) 102 MYX 6. 6e-26 45/92 98 U43549 MC030R 92 MCV subtype 1 1. 5e-20 33/53 48 (Senkevich et al., 1997) 46 orf virus 1. 3e-06 16/29 62 (Mercer et al., 1995) 048L 40360 479 55. 6 poly (A) polymerase (Gershon et at., 1991) 38921 catalytic subunit EIL 479 VAC 0. 0 478/479 99 (Goebel et al. 1990) EIL 479 VAR-1 0. 0 472/479 98 (Shchelkunov et al. 1995) MC031L 470 MCV subtype 1 1. 5e-177 114/173 65 (Senkevich efai., 1997) 049L 42570 737 85. 9 85. 9k protein (Ahn et al. 1990a) E2L 40357 737 VAC 0. 0 735/737 99 (Goebel et al., 1990) E2L 737 VAR-1 0. 0 7311737 99 (Shchelkunov et al. 1995) MC032L 748 MCV subtype 1 8. 3e-127 59/198 29 (Senkevich et al., 1997) OSOL 43269 190 21. 5 dsRNA dependent PK (Chang et al. 1992) 42697 inhibitor host range (Chang et at., t995b) E3L i90 VAC 1. 4e-129 188/190 98 (Goebel et al. 1990) E3L 192 VAR-BSH 8. 6e-126 111/114 97 (Shchelkunov et al., 1995) 1175 dsRNA specific ADA (rat) 7. 2e-12 22/47 46 (O'Connell et al., 1995) 1226 dsRNA specific ADA (human) 2. 8e-09 21/47 44 (Kim et aL 1994) 551 human protein kinase p68 3. 8e-05 22/42 52 (Meurs et al. 1990) INF inducible kinase family >0. 00099 051L 44103 259 29. 8 RNA polymerase subunit (Ahn et al. 1990a) 43324 rpo30, VITF-1 (Broyles and Pennington, 1990) E4L 259 VAC 1. 6e-182 258/259 99 (Goebel et at., 1990) E4L 259 VAR-BSH 3. 2e-180 255/259 98 (Shchelkunov er al.. 1995) MC034L 444 MCV subtype 1 1. 2e-84 107/171 62 (Senkevich et al., 1996) 39 orf virus 6. 7c-10 21139 53 (Mercer et al. 1995) 243 African swine fever virus 0. 00034 17/36 47 (Vydelingum et al 1993) TFIIS family <0. 0096 052R 44180 331 39. 1 39. 1k protein (Goebel et al.. 1990) E5R 45175 331 VAC 1. 2e-235 329/331 99 (Goebel et al., 1990) ESR 341 VAR 3. 1e-223 312/331 94 (Shchelkunov et al. 1995) 332 Taterapox 7. le-225 300/314 95 (Douglas and Dumbell, 1996) 329 Camelpox 1. 4e-221 206/220 93 (Douglas and Dumbell, 1996) 319 Cowpox 1. 5e-202 271/303 89 (Douglas and Dumbell, 1996) 256 Ectromelia 3. 8e-153 218/245 88 (Douglas and Dumbell, 1996) MC038R 276 MCV subtype 1 8. 3e-109 94/152 61 (Senkevich et al., L997) 053R 45312 567 66. 7 66. 7k protein (Goebel ef al. 1990) ORF'START AA"kDa'name/ (putative) BLAS3'° BLAST HSS references STOP function/homologiesg expecl AA id (%) left terminal region : E6R 567 VAR 0. 0 5551567 97 (Shchelkunov er at., 1995) MC037R 565 MCV subtype 7. 2e-247 258/451 57 (Senkevich et al., 1997) 054R 47082 166 19. 5 17k myristylprotein (Martin et at., 1997) E7R 47582 166 VAC 9. 7e-116 166/166 100 (Goebel er al 1990) E7R 60 VAR-) (BSH : E6. 5R) 2. 7e-36 53/60 88 (Shchelkunov et al., 1995) OSSR 47695 273 31. 9 31. 9k protein (Earl et al., 1986) E8R 48516 273 VAC 4. 5e-195 272/273 99 (Goebel et al., 1990) ESR 273 VAR 9. 9e-192 266/273 99 (Shchelkunov et al., 1993a). MC038R 276 MCV subtype 1 8. 3e-109 941152 97 (Senkevich et al., 1997) 056L 51543 1006 116. 9 DNA polymerase (Earl el al., 1986) E9L 48523 1006 VAC 0. 0 1005110 99 (Goebel et ul., 1990), E9L 1005 VAR BSH 0. 0 06 98 (Shchelkunov e. 1995) 1008 Orf virus 0. 0 598/608 51 (Mercer et aL, 1996 ; 988 FPV 0. 0 199/388 60 (Bh1ns et al., 1987) MC039L 1004 MCV subtype I 0. 0 t79/294 58 (Senkevich et al.. 1997) 964 C. biennis poxvirus 2. 6e-77 175/297 34 (Mustafa and Yuen, 1991) DNA polymerase family >6. 0e-06 28/82 057R 51575 95 10. 9 10. 9k protein (Goebel et al., 1990) EIOR 51862 95 VAC 1. 2e-65 93/95 97 (Goebel et a/., 1990) EIOR 95 VAR 3. 1e-64 90/95 100 (Shchelkunov et al., 1993a) MC040R 101 MCV subtype I 5. 2e-44 58/95 94 (Senkevich et <t1., 1997) 058L 52246 129 14. 9 14. 9k protein (Goebel et at., 1990) EIIL 51857 129 VAC 3. 3e-89 129/129 100 (Goebel et ed., 1990) EIIL 129 VAR 4. 2e-87 125/129 96 (Shchelkunov et al., 1995) MC041L 132 MCV subtype 1 1. 8e-30 31/96 32 (Senkevich etc al., 1997) 059L 52691 152 17. 6 77. 6k protein (fl) (Goebel et til., 1990) OIL 52233 666 VAC 6. 9e-101 151/152 99 (Goebel et aL, 1990) QIL 666 VAR-BSH 3. 4e-92 137/152 90 (Shchelkunov et al., 1995) MC042L 783 MCV subtype 1 I. Se-22 39/105 37 (Senkovlch et dIt., 1997) leu zipper, bipartite nuclear (Goebel et al., 1990) targeting sequence 060}, 54189 405 47. 4 77. 6k protein (f2) (Coebel et a/1990) OIL 52972 666 VAC 5. 8e-277 3991400 99 (Goebel er eii., 1990) QIL 66G VAR-I 1. 7e-269 3R3J400 95 (Sitchelkunov et nl., 1995) MC042L 783 MCV subtype I 2. 7e-51 38/104 36 (Senkevich et cit., 1997) /) 61L 54S55 108 12. 4 glutaredoxin 1 (Ahn and Moss, 1992a) 54229 (Johnson er al., 1991) 02L 108 VAC 2. 0e-74 108/108 100 (Goebel el tI/., 1990) Q2L los VAR 4. 9e-72 104/108 96 (Shchelkunov ei al., 1995) 106 human glutaredoxin 3. 2e-31 49/106 46 (Fernando et al., 1994) glutaredoxin family >9. Oe-OS 062L 55639 312 35. 9 35. 9k protein (Schmitt and Stunnenberg, 1988) lull 54701 312 VAC 4. 7e-208 310/312 99 (Goebel et a/., 1990) KIL 312 VAR-BSH 4. 8e-205 3051312 97 (Shchelkunov et al., 1995) MC044L 310 MCV subtype 1 3. 8e-110 163/307 53 (Senkevich et al., 1996) 1451 transcription initiation 0. 029 10/28 35 (Hansen et al., 1996) protein (S. cerevisiae) 063L 55867 73 8. 5 8. 5k protein (Schmitt and Stunnenberg, 1988) I2L 55646 73 VAC 5. 5e-50 73/73 100 (Goebel et a/., 1990) K2L 73 VAR 5. Se-SO 73/73 loo (Shche) ex a/., 1995) MC045L 72 MCV subtype I 3. Se-18 20133 60 (Senkevich er IT1., 1996) 887 hypothetical yeast protein 8. te-OS 9/24 37 S48422 064L 56677 269 30. 0 DNA binding phospho- (Schmitt and Stullnenberg 1988) 55868 protein (F4L interacting) (Davis and Mathews, 199993) 13L 269 VAC 2. 1e-173 267/269 99 (Goebel et al., 1990) K3L 269 VAR 2. 5e-172 265/269 98 (Shchelkunov ez (tl., 1995) MC046L 288 MCV subtype) 9. 6e-66 611149 40 (Senkevich et al., 1996) 209 FPV 13 protein 8. 4e-35 23/66 34 A48563 065L 59075 771 87. 8 rlhonucleotide reductase (Schmitt and Stunnenberg, 1988) 56760 (large subunit) (Tengelsen et al., 1988) 14L 771 VAC 0. 0 771J771 IOD (Goehel e al., 1990) K4L 771 VAR 0. 0 761/771 98 (Shchclkunov er al., 1995) ribonucieotide red. family >1. 8e-05 0661. 59342 79 8. 8 8. 8k protein (Schmitt and Stunnenberg, 1988) 15L 59103 79 VAC 6. 3e-49 79179 100 (Goebel et a/., 1990) K5L 79 VAR 1. 2e-47 76179 96 (Shchelkunuv ex al., 1995) MC047L 82 MCV subtype 1 2. 6e-17 27/73 36 (Senkcvich et al., 1996) 81 FPV 9. 1k protein 1. 4e-12 13/38 34 (Binns et vl 1988) 321 formate dep. nitrit reductnse 0. 00022 7/18 38 (Fleischmann et al., 1995) protein (H. influenzae) 496 permease (b. subtilis) 0. 00031 12/43 27 gi : 2415386 067L 60509 382 43. 5 43. 5k protein (Schmitt and Stunnenberg, 1988) 16L 59361 382 VAC 8. 6e-268 3821382 100 (Goebel et al., 1990) K. 6L 382 VAR 3. 1e-267 380/382 99 (8hchelkunov et al., 1995) MC048L 406 MCV subtype 1 2. 1 e-99 44/119 36 (Senkevich et al., 1996) ORF'START AA° kDa'name/ (putative) BLAST'BLAST'HSS references STOp iunction/homologiest expect AA id (%) left terminal region : 390 FPV 16 protein t. 4e-86 50/136 36 E48563. P12925 mitochondrial energy (Goebel et az s13) transfer proteins signature 068L 61773 423 49. 0 core protein, (Schmitt and Stunnenberg, 1988) 60502 topoisomerase 11 (Kane and Shuman 1993) 17L 423 VAC 0. 0 4201423 99 (Goebel et al., 1990) K7L 423 VAR 1. 5e-306 419/423 99 (Shchelkunov ez al 1995) MC049L 515 MCV subtype I I. 9e-199 126/207 60 (Senkevich et al. 1996) 421 FPV 17 protein 8. 1e-180 185/340 54 F48563 464 Amsacta moorei poxvirus 3. 2e-14 14/47 29 (Hall and Moyer, 1991) 069R 61776 676 77. 6 NPH. II NTPase RNA (Shuman 1992) 63809 helicase (Koonin and Senkevich. 1992) 18R 676 VAC 0. 0 674/676 99 (Goebel et aL 1990) KSAR 676 VAR 0. 0 6651676 98 (Shchelkunov et aL 1995) MC050R 684 MCV subtype 1 7. 6e-227 144/272 52 (Senkevich et al. 1997) 682 FPV virus 18FPV 4. 2e-206 98/178 55 (Binns et al. 1988) 61 matches mainly to RNA <0. 38 helicase family 070L 65588 591 68. 0 68k protein (Schmitt and Stunnenberg, 1988) CIEL 63813 591 VAC 0. 0 5901591 99 (Goebel et al. 1990) HIL 591 VAR-) 0. 0 582/59t 98 (Shchelkunov et a !" 1995) MC056L 593 MCV subtype 1 1. 2e-217 183/361 50 (Senkevich er al. 1997) 341 FPV 9. 4e-75 45/101 44 H48563 071L 65920 111 12. 8 12. 8k protein (Schmitt and Stunnenberg, 1988) 65585 (Meis and Condit, 1991) G3L lit VAC 7. 6e-74 1111111 too (Goebel et aL, 1990) H3L 111 VAR 2. 4e-71 108111i 97 (Shchelkunov et al., 1995) MC057L 108 MCV subtype 1 0. 00012 15145 33 (Senkevich et al. 1997) 072R 65914 220 25. 8 IBT-dependent protein (Meis and Condit, 1991) G2R 66576 220 VAC 1. 9e-155 220/220 100 (Goebel et al.. 1990) H2R 220 VAR l. le-151 214/220 97 (Shchelkunov et al., 1995) MC058R 246 MCV subtype 1 2. 7e-36 42/135 31 (Senkevich et aL 1997) 073L 66920 124 14. 0 glutaredoxin 2 (Gvakharia et nl., 1996) 66546 membrane protein (lensen et al., 1996) H4L 124 VAR 4. 0e-83 123/124 99 (Shchclkunov et al., 1995) G4L 124 VAC 7. 5e-83 123/124 99 (Goebel et al., 1990) MC059L 126 MCV subtype 1 l. le-21 21/51 41 (Senkevich et al. 1997) 074R 66923 434 49. 9 49. 8k protein (Goebei et aL 1990) CSR 68227 434 VAC 1. 6e-305 432/434 99 (Goebel et al 1990) H5R 434 VAR 1. 9e-299 423/434 97 (Shchelkunov et aL 1995) MC60R 437 MCV subtype 1 I. Oe-55 56/119 47 (Senkevich et al., 1997) 1300 HS CG1 protein 0. 015 22182 26 (Print er al. 1994) 075R 68235 63 7. 3 RNA polymerase subunit (Amegadzie er aL 1992), 68426 rpo7 (Meis and Condit 1991) G5. 5R 63 VAC l. le-40 63/63 100 (Goebel er aL 1990) H5. 5R 63 VAR l. le-39 61/63 96 (Shchelkunov el al., 1995) MC061R 63 MCV subtype 1 9. 3e-27 41/63 65 (Senkevich et al., 1997) 35 matches mainly to RNA <0. 54 polymerases 076R 68428 165 19. 0 18. 9k protein (Goebel et aL 1990) G6R 68925 165 VAC 3. 8e-116 1621165 98 (Goebel er al 1990) H6R 165 VAR 1. Se-116 (64/165 99 (Shchelkunov et al., 1995) MC062R 195 MCV subtype 1 3. 0e-32 27/57 47 (Senkevich et al., 1997) 077L 70005 371 42. 0 42. Ok protein (Schmitt and Stunnenberg, 1988) G7L 68890 371 VAC 5. 2e-255 370/371 99 (Goebel er al., 1990) H7L 371 VAR 7. 1e-255 3691371 99 (Shchelkunov et al., 1995) MC065L 402 MCV subtype 1 2. 0e-109 691145 47 (Senkevich et al., 1997) 078R 70036 260 29. 9 VLTF-1, late transcription (Keck et al. 1990) 70818 factor (Wright et al., 1991) G8R 260 VAC 8. 6-184 259/260 99 (Goebel et al. 1990) H8R 260 VAR- 3. 1e-183 2581260 99 (Shchelkunov et al., 1995) MC067R 260 MCV subtype 1 8. 5e-136 1851260 71 (Senkevich et al. 1997) 260 FPV virus FPO 3. 3e-129 175/250 67 (Binns et al. 1988) 079R 70838 340 38. 9 37k myristylprotein (Martin er al., 1997) C9R 71860 340 VAC 3. 7e-237 317/319 99 (Goebel er al., 1990) H9R 340 VAR 9. 1e-236 315/319 98 (Shchelkunov et al. 1995) MC068R 342 MCV subtype 1 4. 8e-79 59/127 46 (Senkevich et al. 1997) 336 FPV virus FPI 3. 9e-65 59/124 47 (Binns er al., 1988) OSOR 71861 250 27. 3 25k myrlstylprotein (Franke er al. 1990) 72613 IMV virion protein (Martin er al., 1997) LIR 250 VAC 1. 8e-175 250/250 100 (Goebel et al., 1990) MIR 250 VAR 6. 4e-170 249/250 99 (Shchelkunov er aL 1995) MC069R 243 MCV subtype 1 6. 5e-103 145/243 59 (Senkevich et al. 1997) 243 FPV virus FP2 6. 2e-95 128/243 52 (Binns et al., 1988) 212 VAC F9L 1. 6e-0. 7 20/58 34 (Goebel et al., 1990) 212 VAR C13L 3. 1e-0. 7 20/58 34 (Shchelkunov er al. 1995) ORF START AA'kDa name I (putative) BLASTd BLAST HSSf referenecs STOP function/homologiess expect AA iã (To) left terminal region : 213 MCV subtype I MC016L 1. 6e-0. 7 13/57 22 (Senkevich et aL 1997) 215 swinepox 3. 3e-0. 5 15/51 29 (Massung et ol., 1993) 081R 72645 87 10. 3 10. 3k protein (Plucienniczak et al. 1985) L2R 72908 87 VAC 3. 9e-57 87/87 100 (Goebel et al., 1990) M2R 87 VAR 4. 0e-56 85/87 97 (Shchelkunov et at., 1995) MC070R 93 MCV subtype 1 0. 064 18/80 22 (Senkevich er al., 1997) 504 Na'dependent phosphate 6. 9e-OS 10/39 25 (Wilson et al., 1994) transporter C. elegans 233 ATPase subunit T. cruzi 0. 013 16/44 36 U38184 2336 Ca channel rat 5. 2e+0. 2 6/25 24 (Dubel er al. 1992) 2238 Ca2+ channel mouse 7. 1e+0. 2 6/25 24 (Coppola er al. 1994) 1559 ABC transporter yeast 0. 40 12/40 30 X97560 082L 73950 350 40. 6 40. 6k protein (Pluciennicznk er al. 1985) L3L 72898 350 VAC 2. 2e-251 3461350 98 (Goebel et al., 1990) M3L 349 VAR 1. 5e-241 296/306 96 (Shchelkunov er al., 1995) MC072L 310 MCV subtype 1 1. 5e-88 64/136 47 (Senkevich et al., L997) 301 FPV F4 protein l. le-80 58/134 43 (Binns er al. 1988) 083R 73975 251 28. 5 core protein VP8 (Yang and Bauer, 1988) 74730 DNA/RNA binding protein (Baylis and Smith, 1997) L4R 251 VAC 5. 6e-170 2511251 100 (Goebel er aL 1990) M4R 251 VAR 3. 7-169 250/251 99 (Shchelkunov et at., 1995) MC073R 254 MCV subtype 1 1. 7e-76 36/59 61 (Senkevich er aL, 1997) 253 FPV virus FP5 6. 4e-55 29/57 50 (Binns et al., 1988) 084R 74740 128 15. 1 15. 1k protein LSR 75126 128 VAC 14. 0k protein 2. 9e-89 1271128 99 (Goebel er al., 1990) M5R 128 VAR 2. 0-87 125/128 97 (Shchelkunov er al. 1995) 129 FPV FP6 8. 1e-16 19/45 42 (Drillien et al., 1987) MC074R 146 MCV subtype 1 0. 073 10/18 55 (Senkevich et al.. 1997) 152 melatonin receptor D. rerio 0. 44 15/66 222 (Reppert et al. 1995) 085R 75083 153 17. 9 dimeric virion protein (Holzer & Falkner, unpubl.) JIR 75544 153 VAC 6. 0e-103 152/153 99 (Goebel er al. 1990) LIR 159 VAR-I 1. 4e-101 149/153 97 (Shchelkunov et al., 1995) 147 capripox CF7 6. 5e-54 53/90 58 (Gershon and Black, 19S9b) 148 myxoma MF7 4. 8e-51 54/93 58 (Jackson and Butts, 1992) 183 MCV subtype 1 1. 9e-47 47/93 50 (Senkevich et al., 1997) MC075R 148 FPV FP7 1. 3e-35 37/84 44 (Drillien et al. 1987) 086R 75560 177 20. 0 thymidine kinase (Hruby and Ball, 1982) 76093 (Weir and Moss 1983) J2R 177 VAC 5. 7e-125 175/177 98 (Goebel et al., 1990) L2R 177 VAR 2. 7c-122 1701177 96 (Shchelkunov er al. 1995) 38 matches mainly to <0. 18 thymidine kinase family 087R 76159 333 38. 9 poly (A) polymerase su, (Gershon et al. 1991) 77160 2'methyl transferase (Gershon and Moss, 1993) J3R 333 VAC 8. 7e-136 330/333 99 (Goebel et al., 1990) L3R 333 VAR-BSH 9. 8e-233 326/333 97 (Shchelkunov er aL 1995) 338 myxoma 5. 7e-288 247/333 74 (Jackson and Bults. 1990) MC076R 343 MCV subtype l 1. 4e-135 79/144 54 (Senkevich er al. 1997) 308 FPV VP39 1. 7e-96 125/267 46 (Binns et al., 1988) 088R 77075 185 21. 3 RNA pot subunit rpo22 (Broyles and Moss 1986) J4R 77632 185 VAC 1. 2e-125 1851185 100 (Goebel et al. 1990) L4R 185 VAR-BSH 7. 9e-125 182/185 98 (Shchelkunov et aL 1995) 185 myxoma 1. 5e-86 124/185 67 (Jackson and Butts, 1990) MC077R 187 MCV subtype 1 I. 9e-76 73/132 55 (Senkevich er aL 1997) 186 FPV 2. 1e-73 72/135 53 (Binns et al., 1988) OS9L 78101 133 15. 2 15. 2k protein (Plucienniczak et au 1985) JSL 77700 33 VAC 2. 4e-95 1331133 100 (Goebel et al. 1990) LSL 133 VAR-1 2. 4e-94 131/133 98 (Shchelkunov er al. 1995) MC078L 134 MCV subtype 1 5. 7e-45 60/127 47 (Senkevich et al., 1997) 137 FPV 1. 4e-43 60/130 46 (Drillien er al., 1987) 377 VAR-1 A16L (BSH : A17L) 0. 049 7/28 25 (Shchelkunov er al. 1995) 378 VAC A16L 0. 049 7/28 25 (Goebel et al. 1990) 090R 78207 1286 146. 9 RNA pol subunit rpol47 (Broyles and Moss. 1986) J6R 82067 1286 VAC 0. 0 1283/1286 99 (Goebel er al. 1990) L6R 1286 VAR 0. 0 1275/1286 99 (Shchelkunov et al.. 1995) MC079R 1289 MCV subtype 1 0. 0 556/760 73 (Senkevich et al. 1997) 100 matches to RNA pol (large <3. 7e-07 subunit) family 091L 82579 171 19. 7 protein tyrosinelserine (Rosel er aL 1986) 82064 phosphatase (Guan et al., 1991) ) fIL 171 VAC 2. 0e-1i7 1701171 99 (Goebel et al., 1994) 111 171 VAR l. le-114 166/171 97 (Shchelkunov er al., 1995) 171 racoonpox 6. 0e-111 1571171 91 B47452 172 myxoma virus 1. 5e-77 83/138 60 (Mossman cr al. 1995a) 173 rabbit fibroma virus 1. 8e-77 46/80 57 (Mossman et al., 1995a) MC082L 169 MCV subtype 1 1. 4e-65 60/114 52 (Senkevich et al., 1997) protein phosphatase family >2. 8e-05 ORF'START AA"kDa'name/ (putative) BLAST"BLAST'HSS'references STOP function/homologiesN expect AA id (%) left terminal region : 092R 82593 189 21. 5 21. 5k protein 99 (Rosel et aL, 1986) H2R 83162 189 VAC 5. 2e-134 188/189 (Goebel et al., 1990) 12R 189 VAR 1. 4e-133 188/189 99 (Shchelkunov et al. 1995) MC083R 191 MCV subtype l 1. 4e-71 951181 52 (Senkevich er al., 1997) 142 myxoma 1. 3e-65 93/142 65 (Jackson and Butts, 1990) 093L 84139 324 37. 5 immunodominant env (Rosel et aL, 1986) 83165 protein p35 ; IMV (Chertov et al., 1991) membrane-associated (Takahashi et al., 1994) H3L 324 VAC 3. 3e-231 322/324 99 (Goebel et al. 1990) 13L 325 VAR-BSH 1. 7e-225 311/320 97 (Shchelkunov er al. 1995) MC084L 298 MCV subtype 1 l. le-36 38/117 32 (Senkevich et al., 1996) 094L 86527 795 93. 6 RAP 94 (RNA-pol assoc. (Ahn and Moss, 1992b) 84140 transcr. spec. factor) (Kane and Shuman, 1992) H4L 795 VAC 0. 0 791/795 99 (Goebel el al., 1990) 14L 795 VAR 0. 0 780/795 98 (Shchelkunov et al., 1995) MC085L 791 MCV subtype 1 0. 0 327/546 59 (Senkevich er al. 1996) 804 Orf virus 0. 0 96/131 73 (Fleming er al. 1993) 484 FPV LIL protein 2. 4e-181 91/176 51 2209386A 095R 86713 203 22. 3 late transcription factor (Kovacs and Moss 1996) 87324 VLTF-4 (Rosel et at., 1986) H5R 203 VAC 1. 8e-128 202/203 99 (Goebel er al. 1990) 15R 221 VAR 5. 1e-102 91/97 93 (Shchelkunov et al. 1995) 227 orf virus F3R 3. 1e-14 29/69 42 (Fleming er al., 1993) 220 MCV subtype 1 3. 1e-09 28/64 43 (Senkevich er aL 1997) 705 nucleolin Xenopus 0. 00041 18/57 31 (Messmer and Drayer 1993) 31 matches to glu/asp rich E<0. 52 proteins 09fiR 87325 314 36. 7 DNA topoisomerase I (Shuman and Moss. 1987) 88269 (Rosel et al. 1986) H6R 314 VAC 0. 0 314/314 100 (Goebet et al., 1990) 16R 314 VAR-BSH 9. 5e-220 312/314 99 (Shchelkunov er aL 1995) 314 shope fibroma virus 8. 5e-141 119/170 70 (Upton et al., 1990b) 318 orf virus 5. 2e-128 82/138 59 (Fleming et aL 1993) MC087R 323 MCV subtype 1 t. 6e-1. 21 111/202 54 (Senkevich er al. 1997) 316 FPV L3R 2. 9e-113 159/303 52 (Zantinge er al. 1996) 21 matches to topoisomerase family 097R 88306 146 17. 0 17. 0k protein (Rosel et al., 1986) H7R 88746 146 VAC 2. 1e-98 144/146 98 (Goebel er aL 1990) 17R 146 VAR 6. 7e-96 141/146 96 (Shchelkunov et al., 1995) MC088R 143 MCV subtype 1 4. 3e-30 45/115 39 (Senkevich er al. 1997) 098R 88790 844 96. 8 mRNA capping enzyme, (Morgan et al., 1984) 91324 large subunit (Niles er al. 1986) DIR 844 VAC 0. 0 842/844 99 (Goebel er al. 1990) FIR 844 VAR-BSH 0. 0 830/844 98 (Shchelkunov et aL, 1995) MC090R 950 MCV subtype 1 0. 0 322/64 64 (Senkevich et al., 1997) 836 shope fibroma virus 0. 0 243/305 79 (Upton et al., 1991b) 868 ASV NP868R 0. 0033 17/55 30 (Pena er al., 1993) 099L 91723 146 16. 9 structural protein (Niles et au 1986) 91283 (Dyster and Niles, 1991) D2L 146 VAC 5. 9e-98 146/146 100 (Goebel et al., 1990) F2L 146 VAR (BSH : F3L) 1. 5e-97 1451146 99 (Shchelkunov et aL 1995) 143 Rabbit fibroma virus 2. 0e-27 13/33 39 (Upton er al., 1991b) MC091L 170 MCV subtype I l. le-20 19/41 46 (Senkevich er aL. 1996) 100R 91716 233 27. 6 27k structural protein (Dyster and Niles, 1991) D3R 92417 237 VAC 3. 8-167 136/142 95 (Goebel er al., 1990) F2R 237 VAR) : F3R 1. 5e-162 131/142 92 (Shchelkunov et al., 1995) 241 shope fibroma virus 9. 3e-20 271100 27 (Upton et al., 1991b) MC092R 268 MCV subtype I 3. 5e-18 16139 41 (Senkevich et au 1997) 206 rabbit fibroma virus C3 1. 6e-09 26/96 27 (Strayer et aL 1991) 101R 92417 218 25. 1 uracil DNA glycosylase (Upton er au 1993) D4R 93073 218 VAC 1. 4e-157 217/218 99 (Goebel et al., 1990) F4R 218 VAR-BSH 5. le-157 216/218 99 (Shchelkunov et al. 1995) 218 shope fibroma virus 1. 5e-117 1511218 69 (Upton et al., 1993) MC093R 226 MCV subtype ! 8. 4e-91 651113 57 (Senkevich et ! au 1997) 218 FPV FPD4 3. 1e-88 1161216 53 (Tartaglia et al., 1990) 297 uracil DNA glycosylase UL2 0. 019 8114 57 L34064 gallid herpesvirus 1 102R 93105 785 90. 4 90. 4k ATP/GTP binding (Niles et al., 1986) 95462 protein (Shchelkunov er al. 1993c) D5R 785 VAC 0. 0 780/785 99 (Goebel et aL 1990) F5R 785 VAR 0. 0 774/785 98 (Shchelkunov et al., 1995) 786 shope fibroma C5 0. 0 283/450 62 (Strayer et al. 1991) 791 MCV subtype 1 0. 0 184/334 55 (Senkevich er aL 1997) 791 FPV virus FPD5 0. 0 1701345 49 (Tartaglia et al. 1990) MC094R 942 C29E6. 4 C. elegans 0. 72 16/56 28 (Wilson et al., 1994) 103R 95503 637 73. 9 early transcription factor (Broyles and Faster, 1990) 97416 VETF-1 (Gershon and Moss, 1990) ORFx START AA"kDat name/ (putative) BLAST''BLAST HSS'references STOP functinn I homoloCiess eapect AA id (%) left terminal region : D6R 637 VAC 0. 0 6351637 99 (Goebel fI al., t990) F6R 637 VAR-1 0. 0 633/637 99 (Shchelkunov er al., 1995) 635 shope fibroma virus 0. 0 2121262 80 (Strayer et al., 1991) MC095R 635 MCV subtype I 0. 0 199/263 75 (Senkevich et al., 1997) 605 FPV 0. 0 188/263 71 (Binns er ai 1990) (Tartaglia et at., 1990) 648 Choristoneura biennis EPV 2. 7e-08 24172 33 (Yuen er al., 1991) 648 Amsacta moorei EPV 4. 2e-06 24177 31 (Hall and Moyer, 1991) 706 African swine fever virus 1. Se-OS 13138 34 (Yanez et at., 1993) 104R 97443 161 17. 9 RNA polymerase (Ahn er al., 1990b) 97928 subunit rpolS (Quick and Broyles, 1990) D7R 161 VAC 1. 4e-108 160/161 99 (Goebel er al., 1990) F7R 161 VAR 2. 2e-106 156/161 96 (Shchelkunov et al., 1995) 163 rabbit fibroma C8 3. 4e-76 108/161 67 (Strayer er al., 1991) MC097R 161 MCV subtype 1 4. 0e-70 991158 62 (Senkevich et al., 1997) 161 FPV D7 5. 4e-66 95/160 59 (Binns et al., 1990) 105L 98805 304 35. 4 virion transmembrane (Niles and Seto, 1988) 97891 protein, carbonic (Niles et al., 1986) anhyerase-llke (Maa er al 1990) DE 304 VAC 2. 3e-212 297/304 97 (Goebe) et at.,) 990) F8L 304 VAR 2. 5e-209 291/304 95 (Shchelkunov er al., 1995) 304 Camelpox virus l. le-207 290/304 95 X97857 303 Ectromelia virus 2. 2e-207 195/207 94 X97856 304 Monkeypox virus 3. 0e-207 2871304 94 X97855 304 Cowpox virus 9. 8e-206 2851304 93 X97858 Carbonic anhydrase family >4. 9e- 13 106R 98847 213 25. 0 25k mutT-like protein (Koonin. 1993) 99488 (Niles et al., 1986) D9R 213 VAC 1. 6e-146 2121213 99 (Goebel et al., 1990) F9R 213 VAR 5. 3e-145 209/213 98 (Shchelkunov et al., 1995) 218 rabbit fibroma 1. 7e-75 105/203 51 (Strayer er al., 1991) MC098R 212 MCV subtype 1 5. 3e-67 541111 48 (Senkevich et al., 1997) 78 FPV D9 2. 0e-13 25/51 49 (Tartaglia er al., 1990) MC099R 229 MCV subtype 1 0. 0041 13/31 41 (Senkevich er aL, 1997) 248 VAR- FIOR 0. 018 14/32 43 (Shchelkunov et al.. 1995) 225 FPV D10 0. 14 15134 44 (Tartaglia et al. L990) 248 VACDIOR 0. 23 11126 42 (Goebel er al., 1990) 107R 99485 248 28. 9 29k mutT-like protein (Koonin, 1993) 100231 (Niles et al., 1986) DIOR 248 VAC 7. 4e-173 245/248 98 (Goebel er al., 1990) FIOR 248 VAR-I 5. 4e-173 245/248 98 (Shchelkunov et al., 1995) 260 shope fibroma D10 3. 8e-72 96/202 47 (Strayer er al., 1991) MC099R 229 MCV subtype 1 1. 4e-54 441100 44 (Senkevich et al., 1997) 225 FPV D10 l. le-45 45/102 44 (Binns et al., 1990) 218 shope fibroma D9 1. 9e-06 19/54 35 (Strayer et at., 1991) 212 MCV subtype I MC098R 0. 13 12/21 57 (Senkevich et al., 1997) 136 mutator Synechocystis 0. 23 12127 44 D90899 2l3 VACD9R 024 llI26 42 (GoebeletalI990) 213 VAR F9R 0. 24 11126 42 (Shchelkunov et al., 1995) 169 mutator M. jannaschii 0. 39 13125 52 (Bult et al., 1996) IOSL 102127 631 72. 4 nucléoside triphosphate (Broyles and Moss, 1987) 100232 phosphohydrolase 1, (Rodriguez et al., 1986) DNA hellcase (Koonin and Senkevich, 1992) DIIL 631 VAC 0. 0 629/631 99 (Goebel et al., 1990) NIL 631 VAR 0. 0 626/631 99 (Shchelkunov et al., 1995) MCIOOR 634 MCV subtype 1 7. 3e-286 392/627 62 (Senkevich et al., 1996) 637 FPV protein 5 2. 8e-275 2141357 59 S42251 370 Rabbit fibroma C14 protein 1. 8e-176 244/368 66 F36819 648 AmEPV 6. oc- 142 81/159 50 (Hall and Moyer, 1991) 648 Choristoneura biennis EPV l. le-136 81/158 51 (Yuen et al., 1991) 89 Swinepox virus 1. 2e-34 60/89 67 (Massung et at., 1993) 1098 ASF 1. 6e-13 26/89 29 (Baylis et al., 1993) 1085 RAD26 (yeast) S. le-OS 16/45 35 (Huang et al., 1994) 769 HS transcription activator 0. 00093 10/22 45 (Okabe et al., 1992) NTPase family >S. le-5 109L 103025 287 33. 3 mRNA capping enzyme, (Niles er al., 1989) 102162 transcription initiation (Weinrich and Hruby, 1986) factor VITF (Vos et al., 1991) D12L 287 VAC 2. 0e-198 2851287 99 (Goebel t ! al., 1990) N2L 287 VAR 9. 8e-198 284/287 99 (Shchelkunov et al., 1995) 287 Swinepox virus 4. te-160 2201287 76 (Massung et al., 1993) MCIOIL 295 MCV subtype 1 S. 8e-126 1711279 61 (Senkevich et al., 1996) 289 FPV protein 6 3. 4e-1l3 114/215 53 S42252 IIOL 104711 551 61. 9 rifampicin resistance (Tartagiia and Paoletti, 1985) 103056 gene, IMV protein (Weinrich and Hruby. 1986) D13L 551 VAC 0. 0 5511551 100 (Goebel eZ al., 1990) N3L 551 VAR 0. 0 547/551 99 (Shchelkunov et al"1995) 551 Swinepox virus 4. Se-286 357/506 70 (Massung et al., 1993) MC102L 547 MCV subtype I 5. 4e-248 2981494 60 (Senkevich et al. 1996) 552 FPV protein 7 6. 6e-223 182/305 59 S42253 584 Heliothis armigera EPV 9. 5e-51 541107 50 (Osborne et al., 1996) ORF'STAR' AA'kDa name/ (putative) BLAST''BLAST'HSS, references STOP function/homologies'expect AA 1d (% u) left terminal region : IIIL ìO5L87 i50 16. 9 late gene trans-activator, (Weinrich and Hruby, 1986) 104735 VLTF-2 (Keck el cil., 1993) AIL 150 VAC 6. 8e-103 149/150 99 (Goebel et al.. 1990) AIL 150 VAR 6. 8e-103 149/150 99 (Shchelkunov et ul., 1995) MCI03L 169 MCV subtype I 6. 3e-S4 74/147 50 (Senkevich er al., 1996) 154 FPV protein 8 2. 8e-50 50/87 57 S42254 112L 105882 224 26. 3 late gene trans-activator (Weinrich and Hruby, 1986) A2L 105208 VAC (Passarelli et nl., 1996) A2L 224 VAR 1. 3e-158 224/224 100 (Goebel er al., 1990) MC104L 224 MCV subtype 1 1. 3e-158 224/224 100 (Shchelkunov et al., 1995) 228 orf virus 6. 4e-127 172/222 77 (Senkevich B1 al., 1996) 606 6. 8e-30 43/66 65 (Mercer et al., 1995) 113L 106109 76 8. 9 8. 9k protein 105879 76 VAC-WR 1. 6e-47 73176 96 (Weinrich and Hruby, 1986) A3L 76 VAR-BSH (I : A2. 5L) 2. 1e-47 71/76 93 (Shchelkunov X1 b11., 1995) MC105L 70 MCV subtype 1 9. 8e-12 26/63 41 (Senkevich et al., 1996) 114L 108058 644 72. 6 major core protein P4b (Rosel and Moss, 1985) A3L 106124 644 VAC 0. 0 643/644 99 (Goebel et nl., 1990) A4L 644 VAR-BSH (I : A3L) 0. 0 636/644 98 (Shchelkunov er al., 1995) MC106L 675 MCV subtypes 1 8. 9e-272 227/357 63 (Senkevich el (r/., 1996) 657 FPV Major core protein P4b 9. 1e-220 169/299 56 (Binns et al., 1989) 115L 108929 272 29. 9 membrane associated core (Demkowicz etal., 1992) tORll I protein (Cudmore er al., 1996) A4L 2SI VAC l. le-145 180/187 96 (Goebel et Lll., 1990) A5L 271 VAR-BSH (t : A4L) I. le-112 165/178 92 (Shchelkunov et al., 1995) 268 Thermoproteus phage I I. 9e-09 38/127 29 (Neumann and Zillig, 1990) 5179 human mucin 4. 5e-07 34/139 24 (Gum et nt., 1994) many matches to Pro-rich proteins 116R 108967 164 19. 0 RNA pol subunit rpol9 (Ahn et al., 1992) ASR 109461 164 VAC 5. 8e-ll0 164II64 100 (Goebel et al.. 1990) A5R 164 VAR-I (BSH : A6R) 7. 0e-109 162/164 98 (Shchelkunov et al., 1995) MC108R 165 MCV subtype 1 3. 3e-51 S2/t5i 53 (Senkevich et al.. 1997) 167 FPV 3. 3e-51 72/161 44 (Kumar and Boyle. 1990) 54 matches/glu-rich proteins <0. 51 117I. 110576 37 ? 43. 1 l3. lk protein A6L 109458 372 VAC 1. 2e-248 371/372 99 (Goebel er al., 1990) A7L 372 VAR-BSH (1 : A6L) I. le-244 364/372 97 (Shchelkunov et al., 1995) MC109L 461 MCV subtype 1 4. Oe-99 132/'67 35 (Senkevich er al., L996) 339 FPV ORF 2 protein 1. 9e-95 ho/279 39 B60013 118L 112732 710 82. 3 VETF 82k subunit (Gershon and Moss, 1990) A7L 110600 710 VAC 0. 0 708/710 99 (Goebel et a/., 1990) A8L 710 VAR-BSH (I A7L) 0. 0 70017iO 98 (Shchelkunov er al., 1995) MCI IOL 707 MCV subtype I 0, 0 240/374 64 (Senkevich er al., 1996) 119R 112786 288 33. 6 33. 6k protein (Van Meir and Wittek, 1988) A8R IL3652 288 VAC 5. 3e-198 2871288 99 (Goebel et al., 1990) A8R 288 VAR-t (BSH : A9R) 3. 1e-195 284/288 98 (Shcheikunov et al., 1995) MCHIR 435 MCV subtype 1 4. 4e-94 1001169 59 (Senkevich er al., 1997) t 120L tt3929 94 10. 5 1O. Sk protein (Van Meir and Wittek. 1988) AIOL t13645 95 VAR-BSH (1 : A9L) 9. 0e-59 78/79 98 (Shchelkunov et al., 1995) A9L 99 VAC 9. 4e-55 82/91 90 (Goebel et al., 1990) MC112L 128 MCV subtype I I. Oe-29 47/71 66 (Senkevich er al., 1996) 69 orf virus 3. 0e-16 27/45 60 (Mercer e) 11., 1995) 121L 116605 891 102. 2 major core protein P4a (Van Meir and Wittek, 1988) 393p (Vanslyke et n/., l991) AIOL 891 VAC 0. 0 8831891 99 (Goebel er al., I990) AIIL 892 VAR-BSH (I : AIOL) 0. 0 442/463 95 (Shchelkunuv et nl., 1995) MC113L 889 MCV subtype 1 5. 8e-289 99/177 55 (Senkevich er it/.. 1996) 122R 116620 318 36. 1 36. 1k protein (Goebef m ul., 1990) AIIR 117576 318 VAC 3. 5e-212 318/318 100 (Goebel et al., 1990) AIIR 319 VAR-1 (BSH : A12R) 2. 7e-154 242/277 87 (Shchelkunov et nl.. 1995) MCI, 4R 304 MCV subtype 1 2. 9e-98 92/154 59 (Senkevich ei al.. 1997) 148 FPV 4a gene t. 9e-13 18/32 56 A20158 123L 118141 187 20. 0 v3rion protein (Takahashi et al., t994) A12L 117578 192 VAC 4. 8e-127 127/128 99 (Goebel et al.. 1990) At3L 189 VAR-BSH (1 : A12L) 5. 9e-64 101/144 70 (Shchelkunov et al., 1995) MC1I5L 178 MCV subtype 1 5. 9e-37 39/83 46 (Senkevich et al., t996) 124L 118377 70 7. 6 structural protein (Takahashi er al., 1994) 118165 IMV membrane protein (Jensen et a/., 1996) 70 p 8 2. 4e-42 66/69 95 (Goebel et al., 1990) All 68 VAC 4. 1e-20 37/64 57 (Shchelkunov et tit., 1995) A14L VAR-BSH (1 : A13L) LZSI. 118757 90 100 structural proteia (Takahashi er f 1994) 1 123455 INtV membrane protein (Jensen e al., 1996) pl6 ORF'START AA"kDa'name/ (putative) BLAST° BLAST'HSS'references STOP fllnetion/homolOgless expect AA Id t 70) left terminal region : A14L 90 VAC 5. 3e-62 90/90 too (Goebel et al., 1990) A15L 90 VAR-BSH (1 : A14L) 5. 3e-61 88/90 97 (Shchelkunov et al., 1995) MCIISL 94 MCV subtype 1 7. 3e-22 31/72 43 (Senkevich er al., 1996) 125 human interferon inducible 0. 23 15/49 30 (Deblandre et al., 1995) protein 126L 119209 94 Il. 0 llk protein A15L 118925 94 VAC 4. 1e-63 94/94 100 (Goebel er al., 1990) A16L 94 VAR-BSH (I : Al5L) I. Oe-61 92/94 97 (Shchelkunov et al.. 1995) MC120L 96 MCV subtype 1 6. 7e-08 17151 33 (Senkevich et al., 1996) 127L 120326 377 43. 4 35k myrlstylprotein (Martin et al., 1997) A16L 119193 378 VAC 6. 3e-288 327/327 100 (Goebel et al., 1990) A17L 377 VAR-BSH (I : A16L) 1. 5e-283 368/377 97 (Shchelkunov et al., 1995) Mu ! 21L 364 MCV subtype 1 6. Se-110 45/115 39 (Senkevich et al. 1996) 128L 120940 203 23. 0 IMV membrane protein (Krijnse-Locker et al., 1996) 120329 morphogenesis factor (Rodriguez et at., 1995) (Wolffe er al., 1996) A17L 203 VAC l. Oe-141 2011203 99 (Goebel et al., 1990) A18L 203 VAR-BSH (I : A17L) I. Oe-141 201/203 99 (Shchelkunov et al., 1995) MC122L 179 MCV subtype 1 1. 4e-47 36181 44 (Senkevich et al., 1996) 129R 120955 493 56. 8 DNA heliease (Koonin and Senkevich, 1992) 122436 DNA dependent ATPase (Bayliss and Condit, 1995) A18R 493 VAC 0. 0 488/493 98 (Goebel et al., 1990) A18R 493 VAR-) (BSH : A19R) 0. 0 478/493 96 (Shchelkunov et al., 1995) MC123R 694 MCV subtype L 5. 3e-167 203/403 50 (Senkevich et al., 1997) 450 Bacteriophage TS D10 0. 0066 13/36 36 P11107 helicase-like protein 130L 122650 77 8. 3 8. 3kb protein (Goebel et al., 1990) A19L 122417 77 VAC 2. 9e-50 77/77 100 (Goebel et a/., 1990) A19L 76 VAR-I (BSH : A20L) 1. 2e-34 54/64 84 (Shchelkunov et al., 1995) MC124L 78 MCV subtype 1 I. Se-13 14/37 37 (Senkevich et al., 1996) 1721 HS RIZ, zink finger protein 0. 0060 7/16 43 (Buyse et al., 1995) 131L 123004 117 13. 6 13. 6k protein (Goebel el al.. 1990) A21L 122651 117 VAC 5. 3e-83 1171117 100 (Goebel et al., 1990) A22L 117 VAR-BSH (1 : A20L) 7. 2e-82 1151117 98 (Shchelkanov et ctL, 1995) MC125L 114 MCV subtype 1 2. 8e-28 23/41 56 (Senkevich et « 1., 1996) 132R 123003 426 49. 1 49. 1k protein (Goebel er al., 1990) A20R 124283 426 VAC 7. 6e-298 423/426 99 (Goebel et al., 1990) A21R 426 VAR 1. 6e-294 418/426 98 (Shchelkunov er al., 1995) MC126R 476 MCV subtype 1 3. 2e-95 341131 25 (Senkevich et al., 1997) 1118 Pichia klyveri DNA pol 0. 069 12/54 22 Y11606 133R 124213 187 21. 9 21. 9k protein (Goebel et al., 1990) A22R 124776 187 VAR-1 (BSH : A23R) I. le-126 182/187 97 (Shchelkunov et al., 1995) A22R 176 VAC 1. 2e-122 174/176 98 (Goebel et al., 1990) MC127R 282 MCV subtype 1 5. 8e-43 35/85 41 (Senkevich et al., 1997) 134R 124796 382 44. 6 44. 6k protein (Goebel et al., 1990) A23R 125944 382 VAC 4. 2e-269 382/382 100 (Goebel et al., 1990) A23R 382 VARI (BSH : A24R) 1. 7e-265 377/382 98 (Shchelkunov et al., 1995) MC128R 383 MCV subtype 1 3. 5e-136 83/143 58 (Senkevich et al., 1997) 135R 125966 1155 132. 4 RNA pol subunit rpol32 (Hooda-Dhingra et al.. 1990) 129436 (Amegadzie et al 1991b) A24R 1164 VAC 0. 0 794/796 99 (Goebel et al., 1990) 1164 CPX rpol32 0. 0 794/795 99 (Patel and Pickup, 1989) A25R 1164 VAR-BSH (1 : A24R) 0. 0 789/795 99 (Shchelkunov et al., 1995) MC129R 1165 MCV subtype I 0. 0 441/565 78 (Senkevich et al., 1997) 1162 orf virus 0. 0 166/258 64 U33419 101 matches to RNA pol beta <0. 036 subunit family right terminal region : 136L 129638 65 7. 5 150k CPX-ATI (f) (Funahashi et al., 1988) A25L 129441 65 VAC 1. 3e-41 64/65 98 (Goebel et al., 1990) 1284 Cowpox (CPX-ATI) 3. 2e-15 28/30 93 (Funahashi et al., 1988) 137L 130916 230 27. 1 27. 1k protein (f) (Amegadzie et al., 1991a) A30L 130224 498 VAR-BSH (I : A29L) 3. le-158 216/227 95 (Shchelkunov et al., 1995) A26L 322 VAC (ATI flanking protein) 5. 6e-142 195/197 98 (Goebel et al., 1990) MC131L 513 MCV subtype 1 2. 1e-12 19/59 32 (Senkevich et al., 1996) MC133L 546 MCV subtype 1 4. 2e-11 12/40 30 (Senkevich et al., 1996) MC130L 451 MCV subtype 1 2. 3e-10 14/40 35 (Senkevich et al., 1996) 702 VAR-I A28L (BSH : A29L) 0. 0021 12/37 32 (Shchelkunov et al., 1995) 726 Camelpox 0. 051 ll/37 29 (Meyer and Rziha, 1993) 138L 131298 110 12. 5 14k membrane protein (Rodriguez and Esteban, 1987) 130966 EEV protein (Rodriguez and Smith. 1990) fusion protein (Gong et al., 1990) A27L 110 VAC 3. 3e-70 108/110 98 (Goebel et al., 1990) A31L i10 VAR-BSH (I :/A30L) I. le-69 107/110 97 (Shchelkunov et al., 1995) 117 Camelpox virus 1. 5e-69 106/110 96 (Meyer et al., 1994) HO Cowpox virus 1. 6e-69 107/110 97 (Meyer et al 1994) ORF'START AA° kDp° name/ (putatIVe) BLAST° BLAST HSS references STOP function/lomoloics"expect AA id (%) left terminal region : 110 Ectrometia virus 6. 7e-68 tO51110 95 (Meyer et al., 1994) HO Monkeypox virus 8. 3e-67 1031110 93 (Meyer et al., 1994) 89 Orf virus 4. 8e-15 22157 38 (Nnase et ul., 1991) 188 Myxoma virus 2. 5e-12 18/33 54 (Jackson et al., 1996) MC133L 546 MCV subtype I 1. Se-11 26/58 d4 (Senkevich et al., 1996) 148 Capripox virus HM2 protein 2. 6e-10 21142 50 (Gershon et al., 1989) MC131L 513 MCV subtype) 1. 5e-05 18/58 31 (Senkevich et aL, 1996) 139L 131739 146 16. 3 16. 3k protein (Amegadzie et al., 1991a) A28L 131299 146 VAC 1. 7e-103 146/146 100 (Goebel et aL, 1990) A31. 5L 146 VAR-BSH (1 : A31L) 2. 9e-100 1411146 96 (Shchelkunov et aL, 1995) 140 Myxoma virus 1. 3e-55 30152 57 (Jackson et aL, 1996) 140 Capripox virus HM3 protein 3. 3e-55 30/49 61 (Gershon et al., 1989) MC134L 141 MCV subtype 1 l. Oe-53 3t/52 59 (Senkevich et al 1996) 143 Amsacta moorei poxvirus 2. 0e-14 16/36 44 (Hall and Moyer, 1991) 140L 132657 305 35. 4 RNA pol subunit rpo35 (Amegadzie et al., 1991a) A29L 131740 305 VAC 3. 6e-215 3041305 99 (Goebel et al., 1990) A32L 305 VAR-BSH 7. 5e-211 297/305 97 (Shchelkunov et aL. 1995) MC135L 303 MCV subtype I 7. 0e-98 51/103 49 (Senkevich et al., 1996) 126 Capripox virus 2. 2e-54 46/61 75 (Gershon et al., 1989) 141L 132853 77 8. 7 8. 7k protein (Amegadzie et al., 1991a) A30L 132620 77 VAC 5. 5e-48 77177 100 (Goebel et al., 1990) A33L 77 VAR 5. 5e-48 77/77 too (Shchelkunov et al., 1995) MC136L 67 MCV subtype 1 9. 2e-16 18140 45 (Senkevich et al., 1996) 142R 133013 125 14. 4 14. 4k protein (Smith et al. 1991) A31R 133390 124 VAC 2. 0e-84 118/124 95 (Goebel et ai, 1990) A34R 140 VAR 1. 6e-79 111/114 97 (Shchelkunov etal"1995) MC138R 117 MCV subtype 1 6. 2e-24 39/98 39 (Senkevich et al., 1997) 143L 134169 269 30. 8 30. 8k protein (Smith et aL, 1991) 133360 ATP/GTP binding motif A (Koonin et au 1993) A32L 300 VAC 6. 4e-190 2681269 99 (Goebel et aL. 1990) A35L 270 VAR 1. 6e-186 263/269 97 (Shchelkunov et au 1995) MC140L 249 MCV subtype 1 7. 6e-95 58/94 61 (Senkevich et al., 1996) 144R 134287 185 20. 6 EEV glycoprotein (Roper et al 1996) A33R 134844 185 VAC 2. 1e-124 1821185 98 (Goebel et al 1990) A36R 184 VAR 1. 8e-121 103/112 91 (Shchelkunov et al., 1995) ISS Ectromelia 2. Se-113 1651185 S9 (Roper et aL. 1996) 145R 134868 168 19. 6 EEV glycoprotein (Duncan and Smith, 1992a) 135374 virulence factor (Mclntosh and Smith, 1996) actln microvilli inducer (Wolffe et al., 1997) A34R 168 VAC 1. 2e-117 165/168 98 (Goebel et al., 1990) A37R 168 VAR-I 1. 7e-117 164/168 97 (Shchelkunov et al., 1995) 167 FPV ORFs BamHI 2, 8. 11 hepatic <0. 056 16/66 24 (Tomley et al., 1988) lectins homologs 199 HS early T-cell activation 0. 0038 12/38 31 (Hamann et al., 1993) antigen CD69 MC143R 159 MCV subtype 1 0. 080 12148 25 (Senkevich et al., 1997) 17 matches to lectins 146R 135418 176 20. 0 20. 0k protein (Smith et al., 1991) A35R 135948 176 VAC H4e-126 1761176 100 (Goubel et al., 1990) A38R 60 VAR-I 2. 9e-37 57/60 95 (Shchelkunov et al., 1995) MC145R 233 MCV subtype 1 1. 23-07 18/55 32 (Senkevich et al.. 1997) 147R 136015 208 23. 8k EEV membrane protein (Parkinson and Smith, 1994) 136641 virulence factor (Smith et al., 1991) A36R 221 VAC 2. 8e-143 140/141 99 (Goebel et al., 1990) A39R 216 VAR 2. 1e-89 138/177 77 (Shchelkunov et al 1995) 19 matches to asn/ser-rich <0. 41 proteins 148R 136705 263 29. 8 29. Sk protein A37R 137496 263 VAC 6. 8e-183 261/262 99 (Goebel et al., 1990) A40R 68 VAR 4. 9e-37 61/67 91 (Shchelkunov et al 1995) 149L 138589 277 31. 5 31. 5k protein (Amegadzie et al., 1991a) A38L 137756 277 VAC 9. 3e-198 274/277 98 (Goebel et at., 1990) A41L 277 VAR t. 6e-187 259/277 93 (Shchelkunov et al., 1995) 303 Rattus norvegicus CD47 3. 9e-24 23/86 26 (Nishiyama et al 1997) 324 MM integrin assoc. protein l. Oe-21 23186 26 (Lindberg et al., 1993) 323 human CD47 precursor 5. 0e-19 28/86 32 (Campbell et al 1992) 150R 138606 83 9. 4 semaphorin-like protein (Kolodkin et al., 1993) 138857 (fl) A39R 403 VAC 8. 0e-46 73/76 96 (Goebel et al., 1990) A42R 74 VAR-1 8. 6e-44 67/71 94 (Shchelkunov et al., 1995) IS1R 139163 210 23. 9 semaphorin-like protein (Kolodkin et al., 1993) 139795 (f2) A39R 403 VAC 3. 0-147 209/210 99 (Goebel et al., 1990) A43R 139 VAR (I : A44R) 1. 8e-68 91/105 86 (Shchclkunov et al., 1995) 653 semaphorin-like protein 1. 7e-20 29/79 36 (Ensser and Fleckenstein, 1995) Alcelaphine herpesvirus 37 matches to semaphorin ORF START AA"kDa name/ (putative) BLAS°f° BLAST'HSS references STOP function/homolvies expect AA ld (%) left terminal region'. /collapsin gene family 152R 139821 168 19. 4 NK celt receptor homolog (Scheiflinger et al., unpubl.) 140327 tectin-Iike protein (Smith er al., 1991) A40R 168 VAC 6. 6e-97 134/I37 97 (Goebel et al., 1990) A45R 6) VAR-f (BSH : A43. SR) 9. 6e-36 54/59 91 (Shcheikunov et al., 1995) 233 HS natural killer (NK) cell 4. 5e- 11 20174 27 (Houchins et al., 1991) protein group 2-A H 240 HS type fui membrane protein 6. 9e-H 16/36 44 (Adamkiewicz er at., 1994) 182 MM NK cell receptor S. 5e-09 16/36 44 (Giorda etc ;.. 1992) 179 HS CD 94 i. 7e-07 111129 37 (Chang et al., 1995a) l27 matches to lectins including NK cell surface proteins and snake venoms 153L 141025 219 25. 1 25. 1k protein (Smith et ai., 1991) All 140366 2l9 VAC 1. 9e-158 218/219 99 (Goebe (et af"1990) A44L 218 VAR-BSH (I : A46L) 1. 4e-152 152/159 95 (Shchelkunov et al., 1995) 244 VAC B29R/C23L 0. 0076 12/53 22 (Goebel et al., 1990) 258 Rabbit fibroma virus Ti 0, 057 13149 26 (Upton et al., t987) 154R 141197 128 14. 5 proftlin-like protetn (Blasco et al., 1991) 141583 (Smith el al., 1991) Aux 133 VAC 1. 2e-87 85187 97 (Goebel et al., 1990) A47R 133 VAR- [ (BSH : A45R) t. 4e-85 82/87 94 (Shchelkunov et al., 1995) 140 HS profilin 2. 2e-23 19/45 42 (Kwiatkowski and Bruns. 1981 10 matches profilin family 155R 141621 190 22. 1 c (ass I membrane (Smith et al., 1991) 142193 glycoprotein (Duncan and Smith, 1992b) A43R 194 VAC (. 5e-137 l62/164 98 (Goebel et al., 1990) A48R 195 VAR-I (BSH : A46R) 1. 9e-128 1011109 92 (Shchelkunov et al., 1995) 51 HS leukocyte antigen 0. 096 7/23 30 X79517 156R 142201 78 8-8 S. Sk protein (Smith et al., 1991) L42437 78 VAC-WR SaIF6R 3. 9e-45 78/78 I00 (Smith er al.. 1991) 258 rabbit myosin heavy chain 0. 00048 13/39 33 A02985 144 matches to various asp/gtu/tys-rich proteins 157L 143577 346 39. 4 313-hydroxysteroid (Moore and Smith, 1992) 142537 dehydrogeause (313-HSD) (Blasco el al., 1991) A44L 346 VAC 4. Se-249 342/346 98 (Goebel er al., 1990) A47C. 210 VAR-BSH (1 : A49L) 1. le-136 185/195 94 (Shchelkunov et al., 1995) MC152R 354 MCV subtype I 9. 2e-104 123/272 45 (Senkevich er al., 1996) 369 FPV 3. 1e-83 33/85 38 (Skinner et al., 1994) matches to dihydroflavonot >2. se-os (Baker and Btasco, 1992) reductases, cholesterol dehydrogenases, UDP- gal actoic-4-epimernses 158R 143624 121 13. 3 superoxide dismutase-like (Blasco et al., t991) 143989 protein (Smith et al., 1991) A45R 125 VAC 2. tue-82 94/96 97 (Goebel et al., 1990) AitR 125 VAR-1 BSH A48R l. le-82 93/96 96 (Shchelkunov er al., 1995) l17 matches with superoxide <0. 027 distnutase famity 159R 143979 2A1 27. 6 27. 6k protein (Smith er al., 1991) AM t4470i 214 VAC 9. 6e-167 238/240 99 (Goebel et al., 1990) A52R 240 VAR-1 (BSH : A49R) 5. 6e-164 233/240 97 (Shchelkunov et al., 1995) 160L 145465 238 27. 6 27. 6k protein (Goebel et al., I990) J1L 144749 244 VAR 5. 1 c-146 114/127 89 (Shchelkunov et al., 1995) A47L 244 VAC 8. 2e-135 121/127 95 (Goebel et al., 1990) integrin tipid binding motif (Smith et al., 1991) 161R 145564 204 23. 2 thymidytate kinasc (Smith et al., 1991) A48R 146178 204 VAC 5. 2e-I40 204/204 f00 (Goebel et al., 1990) J2R 205 VAR 1. 1e-l37 161l165 97 (Shchelkunov er al.. 1995) 16 matches to thymidylatc <0. 49 kinase family 162R t46202 162 18. 8 18. 8k protein (Smith et al., 1991) A49R 146690 162 VAC 6. 0e-106 I59/t62 98 (Goebel et al., 1990) J3R 162 VAR 2. 4e- 103 1541162 95 (Shchelkunov e : al., 1995) 163R 146722 552 63. S ONA tigase (Kerr and Smith, 1989) ASOR 148380 552 VAC 0. 0 547/552 99 (Goebel et al., L990) J4R 552 VAR-1 0. 0 5371552 97 (Shelelkunov rt al., 1995) 922 HS DNA Iigase III 2. 1e-235 102/l65 6 ( (Wei et a (.,) 559 shope fibroma ligase 9. 9e-213 95/200 47 (Parks et al., 1994) 564 FPV ligase 3. 0e-195 1011170 59 (Skinner e1 al., t994) 31 matches mainly to DNA N. 029 ligase family 164R 148426 310 34. 9 34. 9k protein (Antoine et aL, 1996) Air 149358 334 VAC 1. 5e-217 267/274 97 (Goebel et ul., 1990) JAR 334 VAR 9. 1 a-208 251/274 91 (Shchelkunov et al., 1995) ORF START AAb kDa name/ (putative) BLASTd BLAST HSSf referenees STOP function homologies'expect AA td (%) left terminal region : fusion of ASIRIA55R ORFs (Antoine et al., 1996) 165R 149416 315 34. 8 hemagglutinin (Shida, 1986) A56R 150363 315 VAC 1. 8e-211 312/315 99 (Goebel et al 1990) J9R 313 VAR-l (BSH : J7R) 4. 3e-178 183/238 76 (Shchelkunov et al., 1995) 310 raccoonpox l. 5e-91 74/104 71 (Cavallaro and Esposito, 1992) 124 matches to various <0. 34 proteins 166R 150659 97 11. 4 guanylate kinase (f) (Smith et al., 1991) A57R 150952 151 VAC 3. 2e-62 94/97 96 (Goebel et aL 1990) J10R 151 VAR (BSH : J8R) 2. 2e-57 S8/97 90 (Shchelkunov et al., 1995) 198 MM guanylate kinase 4. 3e-24 39/91 42 (Brady et aL 1996) 197 HS guanylate kinase 2. 8e-20 35/91 38 (Brady el al., 1996) 21 matches mainly to <0. 20 guanylate kinases 167R 151103 300 34. 3 serine/threonine protein (Howard and Smith, 1989) 152005 kinase (Banham and Smith, 1992) (Lin et al., 1992) BIR 300 VAC 7. 1e-215 298/300 99 (Goebel el aL, 1990) BIR 300 VAR-I 2. 7e-210 2891300 96 (Shcheìkunov et al. 1995) 283 VAC B12R 4. 9e-49 27/53 50 (Goebel et al. 1990) 100 matches mainly to protein <0. 00031 kinase family 168R 152144 96 11. 5 24. 6k protein (fl) B2R 152434 219 VAC 8. 5e-38 54/60 90 (Goebel et aL 1990) 149 histone H2A pea 0. 59 16150 32 P40281 169R 152289 143 16. 1 24. 6k protein (f2) (Goebel et al. 1990) B2R 152720 219 VAC 5. 7e-86 124/128 96 (Goebel et aL 1990) 170R 152917 179 20. 9 20. 9k protein (f) B3R 153456 124 VAC 8. 2e-33 51/56 91 (Goebel et aL 1990) 167 VAC WR 5. 3e-45 51/56 91 (Smith et al., 1991) 92 VAR-GAR HSR 3. 4e-06 19/28 67 U18339 171R 153683 177 21. 4 65k ank-like protein (Howard et al. 1991) 154216 virulence factor (fl) (Mossman et al., 1996) B4R 558 VAC 8. 5e-107 151/154 98 (Goebel et al. 1990) B6R 558 VAR-1 (BSH : BSR) 1. 7e-98 140/154 90 (Shchelkunov et al 1995) 172R 154107 409 47. 7 65k ank-like protein (Howard et al. 1991) 155336 virulence factor (f2) (Mossman et al., 1996) B4R 558 VAC 2. 4e-283 195/201 97 (Goebel et al., 1990) B6R 558 VAR-t (BSH : BSR) 2. 3e-270 185/201 92 (Shchelkunov et al. 1995) 483 MYX M-T5 protein 5. 5e-10 19/57 33 (Mossman et aL 1996) 1765 MM ankyrin 3 9. 7e-10 22/54 40 (Peters et al. 1995) 516 orf virus 1. 8e-09 16/47 34 U34774 574 VAC B18R 3. 3e-09 11/23 47 (Goebel er aL 1990) 574 VAR-I B19R 3. 6e-09 19/72 26 (Shchelkunov et al., 1995) 882 HS KIAA0379 5. 1e-09 20/52 38 AB002377 668 CPX host range gene 1. 7e-08. 14/47 29 (Spehner et al., 1988) 237 VAC WR hr gene 2. 8e-08 15/47 31 (Kotwal and Moss, 1988a) 472 VAC MIL 5. 1e-07 23181 28 (Goebel et al., 1990) 474 CPX01L 8. 7e-07 22/61 36 (Safronov et al. 1996) 446 VAR OIL 8. 8e-07 23/81 28 (Shchelkunov et aL, 1995) 437 CPXDIL 1. 7e-06 8/27 29 (Safronov et al., 1996) 634 VACC9L 7. 8e-05 (Goebel et al. 1990) 159 matches including ankyrin proteins 173R 155424 317 35. 1 ps/hr protein/ (Takahashi-Nishimaki et al., 1991) 156377 EEV gp42 (Engelstad et al., 1992) complement control protein (Isaacs et al. 1992) B5R 317 VAC 1. 6e-232 312/317 98 (Goebel et al., 1990) B7R 317 VAR-1 (BSH : B6R) 7. 1e-220 294/316 93 (Shchelkunov et al. 1995) 259 CPXD17L 2. 1e-12 16/52 30 (Safronov ez au, 1996) 186 matches to complement <7. 7e-05 control protein family 174R 156474 173 20. 2 20. 2k protein B6R 156995 173 VAC 1. 5e-121 173/173 100 (Goebel et al., 1990) B7R 65 VAR-BSH (I : B8R) 6. 0e-40 62/65 95 (Shchelkunov et aL 1995) 685 NAD-protein ADP ribosyl-0. 56 17/56 30 SXBPT4 transferase phage T4 175R 157033 177 20. 7 20. 7k protein B7R 157566 182 VAC 7. 8e-129 95/108 87 (Goebel et al 1990) 184 VACC8L 0. 16 9/44 20 (Goebel et al., 1990) 182 CPX D12L 0. 49 8/36 22 (Safronov et al. 1996) EF-hand calcium-binding domain 176R 157621 226 26. 0 31k interferon-gamma (Upton et al., 1992) 158301 receptor (f) (Alcami and Smith, 1995) BER 272 VAC 3. 3e-164 1161123 94 (Goebel er al. 1990) B8R 266 VAR-BSH (I : B9R) 3. 0e-153 1111123 90 (Shchelkunov et al., 1995) 266 BCT 2. 6e-151 110/123 89 (Mossman et at., 1995b) 274 swinepox C6 3. 2e-09 12/31 38 (Massung et al 1993) ORF'START AA"kDa'name/ (putative) BLAST'LAST'HSS'references STOP function/homologiess expect AA Id (%) left terminal region : 177R 158458 72 8. 3 8. 3k protein B9R 158676 77 VAC 3. 0e-49 60/60 100 (Goebel et aL 1990) 240 capripox T4 protein 1. 2e-09 16/44 36 M28823 237 shope fibroma virus 0. 0057 15/50 30 F43692 178R 158639 158 17. 9 17. 9k protein BIOR 159115 166 VAC 4. 7e- 110 146/146 100 (Goebel et al., 1990) 530 swinepox VC04 0. 040 13/42 30 (Massung et al. 1993) 689 kelch protein D. melanogaster 0. 14 12/54 27 (Xue and Cooley, 1993) (Senkevich et al., 1993b) 179R 159187 74 8. 5 8. 5k protein BIIR 159411 88 VAC 9. 2e-43 70/73 95 (Goebel et al., 1990) 177 matches to glu/asn rich proteins 180R 159478 283 33. 3 protein kinase (Howard and Smith, 1989) B12R 160329 283 VAC 1. 8e-207 282/283 99 (Goebel et al., 1990) B12R 134 VAR-I 8. 7e-26 31/54 57 (Shchelkunov et al 1995) 300 VACBIR 1. 7e-54 26153 49 (Goebel et aL 1990) 300 VAR-1 BIR 7. 7e-53 25153 47 (Shchelkunov et al,. 1995) t20 matches mainly to protein <0. 34 kinase family 18IR 160437 It6 13. 0 ICE inhibitor/SPI-2 (fl) (Kotwal and Moss. 1989) 160787 (Smith et al., 1989) B13R VAC (Ray et al. 1992) B13R 116 VAR-I (BSH : B12R) 3. 0e-72 1111116 95 (Goebel et al., 1990) 344 CPX crmA 2. 7e-69 105/li4 92 (Shchelkunov es aL 1995) 341 VAC C12L (SPI-1) 2. 8e-39 66/100 66 (Pickup et al. 1986j 353 Ectromelia serpin 2. 1e-23 25/34 73 (Goebel et al., 1990) 344 rabbitpox SPI-I 9. 2e-23 24/34 70 (Senkevich et al., 1993b) 357 CPX SPI-I S. Se-22 25/34 73 (Ali et aL, 1994) 355 VAR-I B25R (BSH : B21R) 1. 4e-21 25/36 69 (Ali et al. 1994) 372 CPX serpin-like protein 1. 7e-21 25I3d 73 (Shchelkunov el at., 1995) 372 135 matches mainly to serpins 1. 7e-36 25/36 69 (Ali et al., 1994) <0. 12 182R 160762 222 24. 9 ICE Inhibitor/SPI-2 (f2) see above B14R 161430 222 VAC 6. 2e-158 218/222 98 (Goebel et al. 1990) 345 VAC WR 9. 4e-156 215/221 97 (Kotwal and Moss, 1989) 345 rabbit pox SPI-2 1. 6e-153 211/221 95 (Ali et al., 1994) 341 CPXcrmA 4. 5e-148 203/220 92 (Pickup et aL 1986) B13R 344 VAR-1 (BSH : B12R) 1 5e-146 203/220 92 (Shchelkunov et aL 1995) 309 matches see above <1. 3e-21 183R 161506 143 16. 7 16. 7k protein (Smith and Chan, 1991) B15R 161937 149 VAC 3. 6e-105 97/98 98 (Goebel et al., 1990) B14R 149 VAR-1 (BSH : B13R) 9. 1e-104 95/98 96 (Shchelkunov et al., 1995) 153 VAR-1 D1L (BSH : D2L) 8. 8e-31 25/52 48 (Shchelkunov es aL 1995) 181 VAC C16UB22R l. Oe-26 25/52 48 (Goebel et al., 1990) 159 capripox T3A 1. 4e-17 17/42 40 (Gershon and Black, 1989a) 151 rabbit fibroma T3A 2. 6e-07 17/44 38 (Upton et al. 1987) 190 VAC A52R 0. 073 10/28 35 (Goebel et al. 1990) 149 VACWRK7R 0. 21 7/22 31 (Boursnell et al. 1988) 149 VAR-IC4R 0. 30 7/22 31 (Shchelkunov et aL 1995) 161 CPXM6R 0. 51 7/22 31 (Safronov et al., 1996) 184R 162021 326 36. 6 interleukin-lB receptor (Alcami and Smith, 1992) 163001 (LL-1aR) (Spriggs et aL 1992) 326 VAC-WR B15R 2 8e-229 323/326 99 (Smith et aL 1991) 326 CPXB16 2. 3e-217 306/326 93 (Spriggs et al. 1992) B16R 290 VAC 4. 4e-202 287/290 98 (Goebel et al., 1990) B17R 69 VAR-1 (BSH : deleted) 8. 1e-38 59/68 86 (Shchelkunov et al. 1995) 296 HS type 11 IL-1 receptor 1. 7e-36 28/75 37 U64094 271 matches mainly to IL-1 <0. 011 receptors, growth factor receptors and Ig family proteins 185L 164069 340 39. 6 39. 6k protein B17L 163047 340 VAC 4. 8e-248 335/340 98 (Goebel et al., 1990) B15L 340 VAR-BSH (I : B18L) 2. 7e-241 325/340 95 (Shchelkunov et al. 1995) 186R 164209 574 68. 0 68k ank-like protein (Smith et al., 1991) BIBR 165933 574 VAC 0. 0 560/574 97 (Goebel et ai 1990) B19R 574 VAR-t (BSH : B16R) 0. 0 539/574 93 (Shchelkunov et aL 1995) I00 matches mainly to <0. 53 poxvirus ankyrin proteins 187R 165999 234 27. 5 surface antigen, (Ueda et al., 1990) 166703 IFN-alpha/beta (Symons et al. 1995) receptor (f) (Colamonici et al., 1995) B19R 353 VAC (WR : B18R) 1. 4e-163 218/233 93 (Goebel et al., 1990) B20R 354 VAR-1 (BSH : B17R) 1. 53-149 Ill/133 83 (Shchelkunov et al 1995) 569 HS interleukin-I receptor 0. 0051 15/43 34 (McMahan et al. 1991) 28 matches mainly to IL-1 <0. 53 receptors 188R 167202 70 8. 2 8. 2k protein (f) ORF START AAb kDa name/ (putative) BLASTd BLAST HSSt references STOP function/homologies'expect AA id (%) left terminal region : B22R 167414 1897 VAR-BSH (I : B26R) 9. 9e-23 31/38 81 (Shchelkunov et al., 1995) 189R 167897 188 21. 7 21. 7k protein B22R 168463 181 VAC B22RIC16L 2. 9e-111 95/104 91 (Goebeì etal. 1990) DIL 153 VAR-I (BSH : D2L) 1. 2e-88 66/71 92 (Shchelkunov et al. 1995) 149 VAC B15R 7. 2e-19 25/52 48 (Goebel et aL 1990) 159 capripox T3A 8. 0e-05 15/45 33 (Gershon and Black, 1989a) 151 VACC6L 0. 25 12146 26 (Goebel et al., 1990). 156 VAR (I : D9LBSH : D12L) 0. 26 12/46 26 (Shchelkunov et al., 1995) 190R/168531 233 26. 9 45k ank-like protein 004L 169232 (f2) B23R 386 VAC (C17UB23R) 6. 2e-159 110/110 100 (Goebel et al., 1990) DIL 91 VAR-BSH 9. 1e-31 46/49 93 (Shchetkunov et al., 1995) 669 CPX host range l. le-13 22/50 44 (Spehner et al., 1988) 452 VAR-1 D6L (BSH : D8L) 1. 7e-11 21/50 42 (Shchelkunov et al.. 1995) 574 VAR-1 B19R (BSH : B16R) 1. 2e-05 22/73 30 (Shchelkunov et al., 1995) 574 VAC B18R (WR : B 7R) 8. 6e-0S 22/73 30 (Goebel et al., 1990) 634 VAC C9L 0. 00011 11124 45 (Kotwal and Moss 1988a) 585 VAR- GIR 0. 00013 22/74 29 (Shchelkunov et al., 1995) 516 orf virus 0. 0088 15/49 30 (Sullivan et al., 1995b) 153 VAR-I D7L (BSH : DIOL) 0. 014 12/28 42 (Shchelkunov et al., 1995) 191R/169309 102 12. 1 45k ank-like protein 003L 169617 (fl) B23R 386 VAC C17UB23R 1. 3e-39 62/63 98 (Goebel et al. 1990) 192R/170305 176 19. 7 secr. TNF receptor (f) (Upton et al. 1991a) 002L 170835 355 CPX crmB 5. 1e-71 76183 91 (Hu et al., 1994) G2R 348 VAR-BSH I. Oe-66 73/83 87 (Shchelkunov et al. 1995) 326 Myxoma virus T2 4. 9e-30 21/37 56 (Upton et al. 1991a) 325 Rabbit fibroma Virus T2 1. 8e-28 17136 47 (Upton et at., 1987) 202 CPXC4L 8. 7e-15 30/51 58 (Heller et al., 1990) B25R 346 HS TNF receptor 1. 9e-08 14/26 53 (Safronov et al. 1996) 259 VAC (CI9L/B25R) 0. 00026 16/19 84 (Goebel et al 1990) 277 human CD40L receptor 0. 0015 11/24 45 (Stamencovic et al., 1989) 30 matches to TNF receptors <0. 39 and surface proteins 193R/171267 136 14. 9 35k major seer. protein (Patel er al. 1990) 001L 171677 chemokine receptor (f) (Graham et al., 1997) B29R 244 VAC (C23UB29R) 6. 0e-57 41/42 97 (Gocbel et nl., 1990) G5R 253 VAR-I 8. 9e-51 46/49 93 (Shchelkunov et al. 1995) 246 CPXORFB 5. 6e-49 40142 95 (Hu et al., 1994) 258 SFV TI protein 2. 5e-20 23/42 54 (Upton et al., 1987) 260 Myxoma virus Tl/35kDa 1. 5e-14 21142 50 (Graham et aL 1997) a Open reading frame coding for at least 65 amino acids (for exceptions see text); minor ORFs located in reverse orientation within large ORFs or ORFs located in the repeat regions of the ITRs (see text) are not listed ; the MVA ORFs (boldface), listed consecutively as appearing in the genome, and homologs in the Copenhagen strain (in italic), in the variola strains and in the molluscum contagiosum, are listed in this row. Split ORFs are boxed. bNumber of deduced amino acids (AA) encoded within an ORF. cPredicted Mr (kDa) for the unmodified protein. d The lowest Poisson probability determined by the BLAST search (Altschul et al., 1990). The Expect value of 0.0 indicates a probability of zero that an alignment occurs by chance ; low Expect values correspond to high homology and vice versa. eAmino acid identity (AA id) of first high-scoring segment pair in the BLASTp protocol.

'Amino acid identity of first high-scoring segment pair (HSS) %.

9 Homologies based on searching PIR and SWISS-PROT databases (BLASTp nr).

"Duplicated ORFs located in ITRs.

Fragment ; complete homologous ORF present in related poxvirus (see reference). j Variola India (I) or variola Bangladesh (BSH) sequences : in cases where the variola sequences are not identical the variola strain first appearing in the blast search protocol is listed. kank, ankyrin.

'HS, homo sapiens. mMM, Mus musculus.

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