Mechanistic Analysis of the Broad Antiretroviral Resistance Conferred by HIV-1 Envelope Glycoprotein Mutations.

ABSTRACT: Despite the effectiveness of antiretroviral (ARV) therapy, virological failure can occur in some HIV-1-infected patients in the absence of mutations in drug target genes. We previously reported that, in vitro, the lab-adapted HIV-1 NL4-3 strain can acquire resistance to the integrase inhibitor dolutegravir (DTG) by acquiring mutations in the envelope glycoprotein (Env) that enhance viral cell-cell transmission. In this study, we investigated whether Env-mediated drug resistance extends to ARVs other than DTG and whether it occurs in other HIV-1 isolates. We demonstrate that Env mutations can reduce susceptibility to multiple classes of ARVs and also increase resistance to ARVs when coupled with target-gene mutations. We observe that the NL4-3 Env mutants display a more stable and cl

SUBMITTER: Hikichi Y 

PROVIDER: S-EPMC7844542 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature