title: Short communication: activation of latent HIV type 1 gene expression by suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor approved for use to treat cutaneous T cell lymphoma.
abstract: The ability of HIV to establish a latent infection causes life-long virus persistence, even after long-term highly active antiretroviral therapy (HAART). The role that latency is playing in preventing clearance of the virus infection has become evident in recent years. Patients who have been successfully treated with ART, having undetectable levels of viral RNA (below 50 copies/ml) in the plasma for years, experienced rapid virus rebound on withdrawal of therapy. Activation of latent proviruses from the infected cells in combination with ART is a therapeutic strategy that may lead to the complete elimination of HIV infection. We report here that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor that has been approved for the treatment of cutaneous T cell lymphoma (CTCL), can activate an HIV-1 vector provirus in a cell model system. Treatment of cells harboring a latent, HIV-1-derived provirus caused activation of both early and late viral gene expression, acetylation of nucleosome on the 5' long terminal repeat (LTR), and remodeling of the chromatin at the 5' LTR. Several compounds, including valproic acid, have been tested for their ability to activate latent HIV-1, but have met with disappointing results. SAHA, a relatively nontoxic, FDA-approved compound, should be considered for developing a strategy to eliminate HIV from patients.
authors.affiliation: Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Edelstein
authors.forename: Sophia
authors.initials: S
authors.lastname: Micheva-Viteva
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Phelan
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Dougherty
mesh_terms: D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008214:Lymphocytes / Q000821:virology*; D011533:Proviruses / Q000187:drug effects; D014775:Virus Activation; D017735:Virus Latency / Q000187:drug effects*; D000077337:Vorinostat
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat
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