HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals
The HIV-1 envelope glycoprotein (Env) is synthesized in the endoplasmic reticulum as a trimeric gp160 precursor, which requires proteolytic cleavage by a cellular furin protease to mediate virus-cell fusion. Env is conformationally flexible but controls its transition from the unbound “closed” confo...
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oai:doaj.org-article:f9a7cfc38dc346768a1d29923cc3a9482021-11-25T19:13:38ZHIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals10.3390/v131122361999-4915https://doaj.org/article/f9a7cfc38dc346768a1d29923cc3a9482021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2236https://doaj.org/toc/1999-4915The HIV-1 envelope glycoprotein (Env) is synthesized in the endoplasmic reticulum as a trimeric gp160 precursor, which requires proteolytic cleavage by a cellular furin protease to mediate virus-cell fusion. Env is conformationally flexible but controls its transition from the unbound “closed” conformation (State 1) to downstream CD4-bound conformations (States 2/3), which are required for fusion. In particular, HIV-1 has evolved several mechanisms that reduce the premature “opening” of Env which exposes highly conserved epitopes recognized by non-neutralizing antibodies (nnAbs) capable of mediating antibody-dependent cellular cytotoxicity (ADCC). Env cleavage decreases its conformational transitions favoring the adoption of the “closed” conformation. Here we altered the gp160 furin cleavage site to impair Env cleavage and to examine its impact on ADCC responses mediated by plasma from HIV-1-infected individuals. We found that infected primary CD4+ T cells expressing uncleaved, but not wildtype, Env are efficiently recognized by nnAbs and become highly susceptible to ADCC responses mediated by plasma from HIV-1-infected individuals. Thus, HIV-1 limits the exposure of uncleaved Env at the surface of HIV-1-infected cells at least in part to escape ADCC responses.Jérémie PrévostHalima MedjahedDani VézinaHung-Ching ChenBeatrice H. HahnAmos B. SmithAndrés FinziMDPI AGarticleHIV-1Env glycoproteinfurin cleavage siteCD4 mimeticsTemsavirnnAbsMicrobiologyQR1-502ENViruses, Vol 13, Iss 2236, p 2236 (2021) |
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HIV-1 Env glycoprotein furin cleavage site CD4 mimetics Temsavir nnAbs Microbiology QR1-502 |
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HIV-1 Env glycoprotein furin cleavage site CD4 mimetics Temsavir nnAbs Microbiology QR1-502 Jérémie Prévost Halima Medjahed Dani Vézina Hung-Ching Chen Beatrice H. Hahn Amos B. Smith Andrés Finzi HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
description |
The HIV-1 envelope glycoprotein (Env) is synthesized in the endoplasmic reticulum as a trimeric gp160 precursor, which requires proteolytic cleavage by a cellular furin protease to mediate virus-cell fusion. Env is conformationally flexible but controls its transition from the unbound “closed” conformation (State 1) to downstream CD4-bound conformations (States 2/3), which are required for fusion. In particular, HIV-1 has evolved several mechanisms that reduce the premature “opening” of Env which exposes highly conserved epitopes recognized by non-neutralizing antibodies (nnAbs) capable of mediating antibody-dependent cellular cytotoxicity (ADCC). Env cleavage decreases its conformational transitions favoring the adoption of the “closed” conformation. Here we altered the gp160 furin cleavage site to impair Env cleavage and to examine its impact on ADCC responses mediated by plasma from HIV-1-infected individuals. We found that infected primary CD4+ T cells expressing uncleaved, but not wildtype, Env are efficiently recognized by nnAbs and become highly susceptible to ADCC responses mediated by plasma from HIV-1-infected individuals. Thus, HIV-1 limits the exposure of uncleaved Env at the surface of HIV-1-infected cells at least in part to escape ADCC responses. |
format |
article |
author |
Jérémie Prévost Halima Medjahed Dani Vézina Hung-Ching Chen Beatrice H. Hahn Amos B. Smith Andrés Finzi |
author_facet |
Jérémie Prévost Halima Medjahed Dani Vézina Hung-Ching Chen Beatrice H. Hahn Amos B. Smith Andrés Finzi |
author_sort |
Jérémie Prévost |
title |
HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
title_short |
HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
title_full |
HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
title_fullStr |
HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
title_full_unstemmed |
HIV-1 Envelope Glycoproteins Proteolytic Cleavage Protects Infected Cells from ADCC Mediated by Plasma from Infected Individuals |
title_sort |
hiv-1 envelope glycoproteins proteolytic cleavage protects infected cells from adcc mediated by plasma from infected individuals |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/f9a7cfc38dc346768a1d29923cc3a948 |
work_keys_str_mv |
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