The crosstalk between ubiquitination and GlcNAcylation of CHAF1A regulates HIV-1 latency and reactivation.

ABSTRACT: The persistence of latent HIV-1 reservoirs remains a critical barrier to cure. Current "shock and kill" strategies are limited by ineffective latency-reversing agents (LRAs) and poor understanding of epigenetic regulation. Here, we identify chromatin assembly factor 1 subunit A (CHAF1A), a histone chaperone enforcing HIV-1 latency, as a therapeutic target regulated by antagonistic post-translational modifications: ubiquitination promotes its degradation, while O-GlcNAcylation stabilizes it. We demonstrate that trifluridine, a Food and Drug Administration-approved antiviral drug, reactivates latent HIV-1 by disrupting O-GlcNAcylation, triggering CHAF1A ubiquitination and proteasomal degradation. Notably, CHAF1A expression increases with age in CD4⁺ T cells (>60 years), correlatin

SUBMITTER: Yang T 

PROVIDER: S-EPMC12724330 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature