Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir.

Details

Serval ID
serval:BIB_047E6CF6A88E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir.
Journal
Cell host & microbe
Author(s)
Rajashekar J.K., Richard J., Beloor J., Prévost J., Anand S.P., Beaudoin-Bussières G., Shan L., Herndler-Brandstetter D., Gendron-Lepage G., Medjahed H., Bourassa C., Gaudette F., Ullah I., Symmes K., Peric A., Lindemuth E., Bibollet-Ruche F., Park J., Chen H.C., Kaufmann D.E., Hahn B.H., Sodroski J., Pazgier M., Flavell R.A., Smith A.B., Finzi A., Kumar P.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Publication state
Published
Issued date
09/06/2021
Peer-reviewed
Oui
Volume
29
Number
6
Pages
904-916.e6
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Small CD4-mimetic compounds (CD4mc) sensitize HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC) by facilitating antibody recognition of epitopes that are otherwise occluded on the unliganded viral envelope (Env). Combining CD4mc with two families of CD4-induced (CD4i) antibodies, which are frequently found in plasma of HIV-1-infected individuals, stabilizes Env in a conformation that is vulnerable to ADCC. We employed new-generation SRG-15 humanized mice, supporting natural killer (NK) cell and Fc-effector functions to demonstrate that brief treatment with CD4mc and CD4i-Abs significantly decreases HIV-1 replication, the virus reservoir and viral rebound after ART interruption. These effects required Fc-effector functions and NK cells, highlighting the importance of ADCC. Viral rebound was also suppressed in HIV-1+-donor cell-derived humanized mice supplemented with autologous HIV-1+-donor-derived plasma and CD4mc. These results indicate that CD4mc could have therapeutic utility in infected individuals for decreasing the size of the HIV-1 reservoir and/or achieving a functional cure.
Keywords
Animals, Antibodies, Neutralizing/immunology, Antibodies, Neutralizing/therapeutic use, Antibody-Dependent Cell Cytotoxicity, Antiviral Agents/therapeutic use, CD4 Antigens/chemistry, CD4 Antigens/metabolism, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, Cell Line, Epitopes/immunology, Female, Glycoproteins/chemistry, Glycoproteins/immunology, HEK293 Cells, HIV Infections/drug therapy, HIV Infections/immunology, HIV Infections/virology, HIV-1/chemistry, HIV-1/drug effects, HIV-1/immunology, Humans, Immunoglobulin Fc Fragments/immunology, Killer Cells, Natural/immunology, Male, Mice, Mice, SCID, Models, Animal, Protein Conformation, Virus Replication/drug effects, env Gene Products, Human Immunodeficiency Virus/chemistry, env Gene Products, Human Immunodeficiency Virus/immunology, CD4i Abs, HIV-1, NK cell, SRG-15, State 2A, antibody-dependent cellular cytotoxicity, envelope glycoprotein, humanized mice
Pubmed
Web of science
Open Access
Yes
Create date
09/05/2023 12:59
Last modification date
29/11/2024 13:38
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