Inhibition of CDK12/CDK13-CYCLIN K rewires P-TEFb signaling to reverse HIV-1 latency and modulate cellular gene expression

ABSTRACT: Persistent HIV-1 latency in long-lived CD4⁺ T-cell reservoirs remains a major obstacle towards viral eradication. Current antiretroviral therapy (cART) exhibits limited clinical efficacy, highlighting the need for new therapeutic interventions. Here, we identify the CDK12/CDK13-Cyclin K (CCNK) complex as a regulator of HIV-1 latency. Pharmacological inhibition of CDK12/CDK13-CCNK with the SR-4835 inhibitor robustly reversed HIV-1 latency in the absence of additional stimuli, both in T cell models and in primary CD4⁺ T cells from people living with HIV-1 receiving cART. Targeting of CDK12/CDK13-CCNK with SR-4835 further synergized HIV-1 latency reversal and enhanced viral reactivation when co-treated with established Latency Reversal Agents. Mechanistically, CDK12/CDK13-CCNK inhibition prom

SUBMITTER: Praveenkumar Murugavelu 

PROVIDER: S-SCDT-10_1038-S44321-026-00536-Z | biostudies-other |

REPOSITORIES: biostudies-other