NF-κB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation

Samuel A. Williams, Lin Feng Chen, Hakju Kwon, Carmen M. Ruiz-Jarabo, Eric Verdin, Warner C. Greene

Research output: Contribution to journalArticlepeer-review


Cells latently infected with HIV represent a currently insurmountable barrier to viral eradication in infected patients. Using the J-Lat human T-cell model of HIV latency, we have investigated the role of host factor binding to the κB enhancer elements of the HIV long terminal repeat (LTR) in the maintenance of viral latency. We show that NF-κB p50-HDAC1 complexes constitutively bind the latent HIV LTR and induce histone deacetylation and repressive changes in chromatin structure of the HIV LTR, changes that impair recruitment of RNA polymerase II and transcriptional initiation. Knockdown of p50 expression with specific small hairpin RNAs reduces HDAC1 binding to the latent HIV LTR and induces RNA polymerase II recruitment. Similarly, inhibition of histone deacetylase (HDAC) activity with trichostatin A promotes binding of RNA polymerase II to the latent HIV LTR. This bound polymerase complex, however, remains non-processive, generating only short viral transcripts. Synthesis of full-length viral transcripts can be rescued under these conditions by expression of Tat. The combination of HDAC inhibitors and Tat merits consideration as a new strategy for purging latent HIV proviruses from their cellular reservoirs.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalEMBO Journal
Issue number1
StatePublished - Jan 11 2006


  • HDAC
  • HIV
  • Latency
  • NF-κB
  • Trichostatin A

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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