title: Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription.
abstract: Numerous studies have looked at the effects of histone deacetylase inhibitors (HDACis) on HIV reactivation in established transformed cell lines and primary CD4(+) T cells. However, their findings remain confusing, and differences between effects of class I- and class II-specific HDACis persist. Because no clear picture emerged, we decided to determine how HDACis reactivate HIV in transformed cell lines and primary cells. We found that neither histone H3 nor tubulin acetylation correlated with HIV reactivation in Jurkat and HeLa cells. Rather, HDACis that could reactivate HIV in chromatin or on episomal plasmids also released free positive transcription elongation factor b (P-TEFb) from its inhibitory 7SK snRNP. In resting primary CD4(+) T cells, where levels of P-TEFb are vanishingly low, the most potent HDACi, suberoylanilide hydroxyamic acid (SAHA), had minimal effects. In contrast, when these cells were treated with a PKC agonist, bryostatin 1, which increased levels of P-TEFb, then SAHA once again reactivated HIV. We conclude that HDACis, which can reactivate HIV, work via the release of free P-TEFb from the 7SK snRNP.
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143-0703.
authors.forename: Koen
authors.initials: K
authors.lastname: Bartholomeeusen
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143-0703.
authors.forename: Koh
authors.initials: K
authors.lastname: Fujinaga
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143-0703; State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143-0703. Electronic address: matija.peterlin@ucsf.edu.
authors.forename: B Matija
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014404:Tubulin / Q000378:metabolism
chemical_list: C476123:HEXIM1 protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014404:Tubulin; D042925:Positive Transcriptional Elongation Factor B
keywords: 7SK snRNP; HEXIM1; HIV; HIV Latency; Histone Deacetylase Inhibitors; Histone Modification; P-TEFb; Transcription Elongation Factors; Tubulin
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