Changes in the V1 Loop of HIV-1 Envelope Glycoproteins Can Allosterically Modulate the Trimer Association Domain and Reduce PGT145 Sensitivity.

ABSTRACT: 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.

SUBMITTER: Cervera H 

PROVIDER: S-EPMC9154022 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature