Year: 2017
Type: article
Abstract: The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20-β21 element as a major regulator of Env transitions. Several amino acid changes in the β20-β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry.
Source: Nature Communications
Institutions: Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Drexel University, Yale University, University of Pennsylvania, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Johns Hopkins University, Cornell University, Weill Cornell Medicine
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: HIV-1 Envelope Glycoproteins, Structure-Based Antagonism of HIV-1 Envelope Function in Cell Entry, G2067081224, G2986651025, G3193714930, G3454215664, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, G4228559406, G5598320952, G5786936113, G6657360324, G6714156533, G7213126365, G759145187, Next-generation fluorescent Probes for Biological research, G9000129325, G9000240603, G9000301437, Conformational Landscape of the HIV-1 Envelope Glycoproteins, Single molecule imaging of HIV-1 entry
OpenAlex ID: W2761820181