Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome

ABSTRACT

Studies of RNA Polymerase II (Pol II) transcription of the HIV-1 genome are of clinical interest, as the insight gained may lead to strategies to selectively reactivate latent viruses in patients in whom viral replication is suppressed by antiviral drugs. Such a targeted reactivation may contribute to a functional cure of infection. This review discusses five Cyclin-dependent kinases – CDK7, CDK9, CDK11, CDK2, and CDK8 – involved in transcription and processing of HIV-1 RNA. CDK7 is required for Pol II promoter clearance of reactivated viruses; CDK7 also functions as an activating kinase for CDK9 when resting CD4⁺ T cells harboring latent HIV-1 are activated. CDK9 is targeted by the viral Tat protein and is essential for productive Pol II elongation of the HIV-1 genome. CDK11 is associated with the TREX/THOC complex and it functions in the 3′ end processing and polyadenylation of HIV-1 transcripts. CDK2 phosphorylates Tat and CDK9 and this stimulates Tat activation of Pol II transcription. CDK8 may stimulate Pol II transcription of the HIV-1 genome through co-recruitment with NF-κB to the viral promoter. Some notable open questions are discussed concerning the roles of these CDKs in HIV-1 replication and viral latency.

KEYWORDS:

• HIV
• CDK
• HIV latency
• Tat
• CDK9
• P-TEFb

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

The author's work was supported by grants from the National Institute of Allergy and Infectious Diseases [AI24866 and AI32001].