Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency

Young Kyeung Kim, Cyril F. Bourgeois, Richard Pearson, Mudit Tyagi, Michelle J. West, Julian Wong, Shwu Yuan Wu, Cheng Ming Chiang, Jonathan Karn

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87 Scopus citations

Abstract

Latently infected cells rapidly initiate HIV transcription after exposure to signals that induce NF-κB. To investigate the role of TFIIH during HIV reactivation in vivo, we developed a population of Jurkat cells containing integrated, but transcriptionally silent, HIV proviruses. Surprisingly, the HIV promoter in unactivated Jurkat T cells is partially occupied and carries Mediator containing the CDK8 repressive module, TFIID and RNAP II that is hypophosphorylated and confined to the promoter region. Significantly, the promoter is devoid of TFIIH. Upon stimulation of the cells by TNF-α, NF-κB and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost. Detailed time courses show that the levels of TFIIH at the promoter fluctuate in parallel with NF-κB recruitment to the promoter. Similarly, recombinant p65 activates HIV transcription in vitro and stimulates phosphorylation of the RNAP II CTD by the CDK7 kinase module of TFIIH. We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency.

Original languageEnglish (US)
Pages (from-to)3596-3604
Number of pages9
JournalEMBO Journal
Volume25
Issue number15
DOIs
StatePublished - Aug 9 2006

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Keywords

  • CDK7
  • HIV latency
  • NF-κB
  • TFIIH
  • Tat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Kim, Y. K., Bourgeois, C. F., Pearson, R., Tyagi, M., West, M. J., Wong, J., Wu, S. Y., Chiang, C. M., & Karn, J. (2006). Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency. EMBO Journal, 25(15), 3596-3604. https://doi.org/10.1038/sj.emboj.7601248