Envelope glycoproteins sampling states 2/3 are susceptible to ADCC by sera from HIV-1-infected individuals.

TitleEnvelope glycoproteins sampling states 2/3 are susceptible to ADCC by sera from HIV-1-infected individuals.
Publication TypeJournal Article
Year of Publication2018
AuthorsPrévost J, Richard J, Ding S, Pacheco B, Charlebois R, Hahn BH, Kaufmann DE, Finzi A
JournalVirology
Volume515
Pagination38-45
Date Published02/01/2018
ISSN1096-0341
Abstract

Recent analysis of HIV-1 envelope glycoproteins (Env) dynamics showed that the unliganded Env trimer can potentially sample three conformations: a metastable "closed" conformation (State 1), an "open" CD4-bound conformation (State 3), and an intermediate "partially open" conformation (State 2). HIV-1 evolved several mechanisms to avoid "opening" its Env in order to evade immune responses such as antibody-dependent cellular cytotoxicity (ADCC), which preferentially targets Envs in the CD4-bound conformation on the surface of infected cells. Here we took advantage of a well-characterized single-residue change in the gp120 trimer association domain to modify Env conformation and evaluate its impact on ADCC responses. We found that cells infected with viruses expressing Env stabilized in States 2/3 become highly susceptible to ADCC responses by sera from HIV-1-infected individuals. Our results indicate that the conformations spontaneously sampled by the Env trimer at the surface of infected cells has a significant impact on ADCC responses.

DOI10.1016/j.virol.2017.12.002
Alternate JournalVirology
PubMed ID29248757
PubMed Central IDPMC5843759
Grant ListR01 AI129769 / AI / NIAID NIH HHS / United States
UM1 AI100645 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
352417 / / CIHR / Canada
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