Conformational activation and disulfide exchange in HIV-1 Env induce cell-free lytic/fusogenic transformation and enhance infection.

ABSTRACT: Disulfide exchange is underexplored as a mechanism influencing HIV-1 entry. Prior studies demonstrated that redox enzyme inhibition can prevent HIV-1 infection but with limited mechanistic explanation. We hypothesize that ligand-driven rearrangement ("conformational activation") enables enzyme-mediated disulfide exchange in Env residues ("disulfide trigger") that promotes fusion transformations, enhancing virus entry. We tested soluble CD4 and CD4-binding site entry inhibitors as conformational activators and the ubiquitous redox enzyme thioredoxin-1 (Trx1) as disulfide trigger. We found that combination treatment caused fusion-like Env transformation and pseudovirus lysis, independent of cells. Notably, only compounds associated with gp120 shedding caused lysis when paired with Trx1. In e

SUBMITTER: Ang CG 

PROVIDER: S-EPMC11915811 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature