PADI4-mediated citrullination of histone H3 stimulates HIV-1 transcription.

ABSTRACT: HIV-1 infection establishes a reservoir of long-lived cells with integrated proviral DNA that can persist despite antiretroviral therapy (ART). Certain reservoir cells can be reactivated to reinitiate infection. The mechanisms governing proviral latency and transcriptional regulation of the provirus are complex. Here, we identify a role for histone H3 citrullination, a post-translational modification catalyzed by protein-arginine deiminase type-4 (PADI4), in HIV-1 transcription and latency. PADI4 inhibition by the small molecule inhibitor GSK484 reduces HIV-1 transcription after T cell activation in ex vivo cultures of CD4⁺ T cells from people living with HIV-1 in a cross-sectional study. The effect is more pronounced in individuals with active viremia compared to individuals un

SUBMITTER: Love L 

PROVIDER: S-EPMC12198384 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature