HIV Transcription Is Independent of Mediator Kinases

AIDS Res Hum Retroviruses. 2019 Aug;35(8):710-717. doi: 10.1089/AID.2019.0039. Epub 2019 May 29.

Abstract

While the roles in HIV transcription of many cyclin-dependent kinases (CDKs) have been well defined, little is known about the impact of mediator kinases (MDKs), CDK8 and CDK19, in this process. Mediator complexes containing CDK8 or CDK19 repress or activate the expression of selected genes. The aim of this study was to investigate the role of MDKs in HIV transcription. siRNA knockdown of both MDKs had no effect on HIV transcription. This result was confirmed using two MDK inhibitors, Cortistatin A (CA) and Senexin A (SnxA). Furthermore, neither CA nor SnxA inhibited viral reactivation in Jurkat cell models of HIV latency. Taken together, these results indicate that MDKs are not required for HIV transcription.

Keywords: CDK19; CDK8; Cortistatin A; HIV transcription; Senexin A; mediator kinases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 8 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 8 / genetics*
  • Cyclin-Dependent Kinase 8 / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Polycyclic Compounds / pharmacology
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Transcription, Genetic / genetics*
  • Virus Activation / drug effects*
  • Virus Latency / drug effects

Substances

  • Polycyclic Compounds
  • RNA, Small Interfering
  • cortistatin A
  • CDK19 protein, human
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases