title: HIV-1 reactivation induced by apicidin involves histone modification in latently infected cells.
abstract: The existence of stable, transcriptionally silent human immunodeficiency virus (HIV) in latently infected cells represents a major obstacle to acquired immune deficiency syndrome (AIDS) therapy. Histone deacetylase (HDAC) can inhibit histone acetylation, resulting in HIV-1 provirus transcription silence. Apicidin, a widely used antiparasitic drug, exhibits antiparasitic activity by inhibiting HDAC. Using the latently infected A10.6 cell line, we describe the dose- and time-dependent manner in which Apicidin reverses HIV-1 latency. We found that Apicidin can synergize with trichostatin A (TSA) to activate HIV-1 gene expression. Chromatin immunoprecipitation (ChIP) assay further indicates that Apicidin induces HIV-1 reactivation by increasing the acetylation levels of H3 and H4 at nucleosome 1 in HIV-1 long terminal repeats (LTR). Our research reveals a potent activator for reactivating latent HIV-1 and shows promise for HIV-1 therapy.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Shiguan
authors.initials: S
authors.lastname: Lin
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Zhu
mesh_terms: D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004357:Drug Synergism; D020869:Gene Expression Profiling; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells; D010456:Peptides, Cyclic / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects* / Q000502:physiology; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; C102351:apicidin; C012589:trichostatin A