Journal
VIROLOGY
Volume 515, Issue -, Pages 38-45Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2017.12.002
Keywords
HIV-1; Envelope glycoproteins; States 2/3; CD4; Non-neutralizing antibodies; ADCC
Categories
Funding
- CIHR Foundation [352417]
- amfAR Innovation Grant [109343-59-RGRL]
- FAIR
- NIH [R01, AI129769, AI100645, AI100663]
- amfAR
- CIHR Fellowship Award
- FRSQ postdoctoral fellowship award
- FRQS Senior Research Scholar Award
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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.
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