Open AccessChanges in the V1 Loop of HIV-1 Envelope Glycoproteins Can Allosterically Modulate the Trimer Association Domain and Reduce PGT145 Sensitivity
Author(s) -
Héctor Cervera,
Sneha Ratnapriya,
Angela Chov,
Alon Herschhorn
Publication year - 2021
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.0c00899
Subject(s) - virology , biology , immunogen , glycoprotein , epitope , allosteric regulation , trimer , infectivity , population , neutralization , human immunodeficiency virus (hiv) , maraviroc , v3 loop , antibody , virus , immunology , genetics , chemistry , monoclonal antibody , medicine , dimer , receptor , organic chemistry , environmental health
Human immunodeficiency virus (HIV-1) envelope glycoproteins (Envs) are a main focus of immunogen design and vaccine development. Broadly neutralizing antibodies (bnAbs) against HIV-1 Envs target conserved epitopes and neutralize multiple HIV-1 viral strains. Nevertheless, application of bnAbs to therapy and prevention is limited by resistant strains that are developed or preexist within the viral population. Here we studied the HIV-1 NAB9 Envs that were isolated from a person who injects drugs and exhibits high and broad resistance to multiple bnAbs. We identified an insertion of 11 amino acids in the V1 loop that allosterically modulates HIV-1 NAB9 sensitivity to the PGT145 bnAb, which targets the Env trimer association domain and supports high level viral infectivity. Our data provide new insights into the mechanisms of HIV-1 resistance to bnAbs and into allosteric connectivity between different HIV-1 Env domains.