Role of the HIV-1 positive elongation factor P-TEFb and inhibitors thereof

Mini Rev Med Chem. 2009 Mar;9(3):379-85. doi: 10.2174/1389557510909030379.

Abstract

Transcription is considered to be a crucial step in the replication cycle of HIV-1. Tat regulates an early step of transcription elongation. The positive elongation factor P-TEFb, a heterodimer containing a catalytic subunit (CDK9) and unique regulatory cyclins (CycT1), is required for HIV-1 Tat transcriptional activation. This is a potential target for new HIV-1 transcription inhibitors. Without P-TEFb, transactivation is restrained and only short transcripts are generated. All the P-TEFb inhibitors can suppress the HIV-1 transactivation process by inhibition of CycT1, CDK9 or their interaction. Several low-molecular-weight compounds such as flavopiridol, roscovitine and the human small nuclear RNA 7SK which have been showed to possess potent anti-HIV activity by interfering with P-TEFb functions are reviewed in this article.

Publication types

  • Review

MeSH terms

  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology*
  • Humans
  • Models, Biological
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Positive Transcriptional Elongation Factor B / antagonists & inhibitors*
  • Positive Transcriptional Elongation Factor B / chemistry
  • Positive Transcriptional Elongation Factor B / physiology*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Purines / chemistry
  • Purines / pharmacology
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / pharmacology
  • Roscovitine
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology

Substances

  • Flavonoids
  • Piperidines
  • Protein Kinase Inhibitors
  • Purines
  • RNA, Small Nuclear
  • Roscovitine
  • alvocidib
  • Positive Transcriptional Elongation Factor B