Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity.
Details
Serval ID
serval:BIB_3DCB9CE4B268
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity.
Journal
EBioMedicine
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Publication state
Published
Issued date
01/2016
Peer-reviewed
Oui
Volume
3
Pages
122-134
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells.
Keywords
Antibody-Dependent Cell Cytotoxicity/immunology, CD4 Antigens/metabolism, CD4-Positive T-Lymphocytes/physiology, CD4-Positive T-Lymphocytes/virology, Cell Communication, Cell Line, HIV Envelope Protein gp120/immunology, HIV Envelope Protein gp120/metabolism, HIV-1/physiology, Humans, Molecular Mimicry, Protein Binding, ADCC, Bystander killing, CD4, CD4-bound conformation, CD4-mimetics, Envelope glycoproteins, HIV-1, Non-neutralizing antibodies, gp120
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
09/05/2023 13:00
Last modification date
29/11/2024 13:32