Membrane HIV-1 envelope glycoproteins stabilized more strongly in a pretriggered conformation than natural virus Envs.

ABSTRACT: The pretriggered conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)₃) is targeted by virus entry inhibitors and broadly neutralizing antibodies (bNAbs). The lability of pretriggered Env has hindered its characterization. Here, we produce membrane Env variants progressively stabilized in pretriggered conformations, in some cases to a degree beyond that found in natural HIV-1 strains. Pretriggered Env stability correlated with stronger trimer subunit association, increased virus sensitivity to bNAb neutralization, and decreased capacity to mediate cell-cell fusion and virus entry. For some highly stabilized Env mutants, after virus-host cell engagement, the normally inaccessible gp120 V3 region on an Env intermediate became ta

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC11228805 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature