Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers

Yang, Zhi; Dam, Kim-Marie A.; Gershoni, Jonathan M.; Zolla-Pazner, Susan; Bjorkman, Pamela J.

doi:10.1128/jvi.01082-22

Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers

Journal Article · Wed Dec 21 00:00:00 EST 2022 · Journal of Virology

DOI:https://doi.org/10.1128/jvi.01082-22· OSTI ID:2423884

^[1]; ^[1]; Gershoni, Jonathan M. ^[2]; ^[3]; ^[1]

California Institute of Technology (CalTech), Pasadena, CA (United States)
Tel Aviv University (Israel)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)

Human immunodeficiency virus type 1 (HIV-1) envelope (Env), a heterotrimer of gp120-gp41 subunits, mediates fusion of the viral and host cell membranes after interactions with the host receptor CD4 and a coreceptor. CD4 binding induces rearrangements in Env trimer, resulting in a CD4-induced (CD4i) open Env conformation. Structural studies of antibodies isolated from infected donors have defined antibody-Env interactions, with one class of antibodies specifically recognizing the CD4i open Env conformation. In this study, we characterized a group of monoclonal antibodies isolated from HIV-1 infected donors (V2i MAbs) that displayed characteristics of CD4i antibodies. Binding experiments demonstrated that the V2i MAbs preferentially recognize CD4-bound open Env trimers. Structural characterizations of V2i MAb-Env-CD4 trimer complexes using single-particle cryo-electron microscopy showed recognition by V2i MAbs using different angles of approach to the gp120 V1V2 domain and the β2/β3 strands on a CD4i open conformation Env with no direct interactions of the MAbs with CD4. We also characterized CG10, a CD4i antibody that was raised in mice immunized with a gp120-CD4 complex, bound to an Env trimer plus CD4. CG10 exhibited characteristics similar to those of the V2i antibodies, i.e., recognition of the open Env conformation, but showed direct contacts to both CD4 and gp120. Structural comparisons of these and previously characterized CD4i antibody interactions with Env provide a suggested mechanism for how these antibodies are elicited during HIV-1 infection.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: Bill & Melinda Gates Foundation; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2423884

Journal Information:: Journal of Virology, Journal Name: Journal of Virology Journal Issue: 24 Vol. 96; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
CD4i antibody
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HIV-1 Env
V2i MAb
Virology
monoclonal antibodies

Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers

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