Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors.

ABSTRACT: Persons with HIV (PWH) receiving integrase (IN) strand transfer inhibitors (INSTIs) have been reported to experience virologic failure (VF) in the absence of resistance mutations in IN. We previously reported that mutations in the viral nucleocapsid (NC) are selected in the presence of the INSTI dolutegravir (DTG) and confer levels of INSTI resistance comparable to those conferred by clinically relevant IN mutations. Here we show that these NC mutations accelerate the kinetics of viral DNA integration. The shortened time frame between the completion of reverse transcription and integration correlates with reduced sensitivity to DTG, suggesting that NC mutations limit the window of opportunity for INSTIs to block viral DNA integration. We find that in primary peripheral blood mononuclear ce

SUBMITTER: Hikichi Y 

PROVIDER: S-EPMC12478370 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature