Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome. Issue 2 (15th March 2019)

• Record Type: Journal Article
• Authors: Rice, Andrew P.
• Is Part Of: Transcription. Volume 10:Issue 2(2019)
• Page Start: 111
• Page End: 117
• Publication Date: 2019-03-15
• Subjects: HIV -- CDK -- HIV latency -- Tat -- CDK9 -- P-TEFb; Genetic transcription -- Periodicals; 572.8
• DOI: 10.1080/21541264.2018.1542254
• Languages: English
• ISSNs: 2154-1264

Abstract

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.