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| Subject Categories: Chromatin & Transcription | Microbiology & Pathogens |
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| The EMBO Journal
(2006) 25, 139–149, doi:10.1038/sj.emboj.7600900 Published online 1 December 2005 |
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NF- B p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation |
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| Samuel A Williams1, 2, Lin-Feng Chen1, 5, Hakju Kwon1, Carmen M Ruiz-Jarabo1, Eric Verdin1, 3 and Warner C Greene1, 3, 4 |
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1 Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA 2 Department of Physiology, University of California, San Francisco, CA, USA 3 Department of Medicine, University of California, San Francisco, CA, USA 4 Department of Microbiology and Immunology, University of California, San Francisco, CA, USA To whom correspondence should be addressed Warner C Greene, Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA. Tel.: +1 415 734 4805; Fax: +1 415 355 0153; E-mail: wgreene@gladstone.ucsf.edu 5 Present address: Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S Mathews Avenue, Urbana, IL 61801, USA Received 30 June 2005; Accepted 15 November 2005; Published online 1 December 2005. |
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| Abstract |
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| 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 B enhancer elements of the HIV long terminal repeat (LTR) in the maintenance of viral latency. We show that NF-B 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. |
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| Keywords: HDAC, HIV, latency, NF-B, trichostatin A |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHCBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency The EMBO Journal Article (12 Dec 2007) CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency The EMBO Journal Article The EMBO Journal Article (02 Apr 2001) |
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