Title:
VIRUS SET POINT FOR REDUCING HUMAN IMMUNODEFICIENCY VIRUS INFECTION, FACTOR FOR RECONSTRUCTING CELLULAR IMMUNITY, AND DRUG APPLICATION
Document Type and Number:
WIPO Patent Application WO/2022/217373
Kind Code:
A1
Abstract:
An application of vMIP-II in effective dissociation of a HIV antigen-receptor trimer complex at an early stage of HIV infection to reduce a virus set point (a stable viral load established after acute infection) and in induction of dephosphorylation of CD8+T cells into Tcm cells, relating to the technical field of biology. By means of research on a Rhesus monkey SIV infection model, it is found that the vMIP-II may release a free gp120 protein by dissociating a gp120-CD4-CCR5 trimer on HIV-target cells at the early stage of HIV infection to protect CD4+T cells. Then, the free gp120 protein may be captured by APC and presented to the CD8+T cells, such that said cells are differentiated into specific effector CD8+T cells, and the content of CD8+Tcm is significantly increased. Moreover, it is found that Tcm proliferation is that the vMIP-II closes a CD8+T chemokine receptor to enable low expression of G protein, thereby reducing an intracellular Ca2+ concentration and a mitochondrial membrane potential, and inhibiting phosphorylation-related genes, such that low expression of phosphorylated protein ERK1/2 and Akt is enabled, a CD8+T phosphorylation signal is weakened, and metabolic reprogramming occurs to convert into Tcm. Therefore, such a novel action mechanism as the vMIP-II for preventing virus RNA from entering a target cell provides a new strategy for research and development of drugs for HIV/SIV-infected AIDS, provides a new target for adoptive immunotherapy against viruses and tumors, and has important clinical application value.
Inventors:
LI SHIYU (CN)
SUN HANXIAO (CN)
WANG YUZHE (CN)
DENG JIANSHAN (CN)
LIU SHUTING (CN)
ZHONG ZHIYIGN (CN)
GENG CHENGXU (CN)
SUN HANXIAO (CN)
WANG YUZHE (CN)
DENG JIANSHAN (CN)
LIU SHUTING (CN)
ZHONG ZHIYIGN (CN)
GENG CHENGXU (CN)
Application Number:
PCT/CN2021/086313
Publication Date:
October 20, 2022
Filing Date:
April 11, 2021
Export Citation:
Assignee:
LI SHIYU (CN)
International Classes:
A61K38/19; A61P29/00; A61P31/18; A61P35/00; C07K14/52; C12N5/0783
Foreign References:
| CN111214650A | 2020-06-02 | |||
| CN111593022A | 2020-08-28 | |||
| CN102146132A | 2011-08-10 | |||
| US20030220482A1 | 2003-11-27 | |||
| CN1277873A | 2000-12-27 | |||
| US20180289689A1 | 2018-10-11 |
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