title: Novel histone deacetylase inhibitor NCH-51 activates latent HIV-1 gene expression.
abstract: Pharmacological manipulations to purge human immunodeficiency virus (HIV) from latent reservoirs have been considered as an adjuvant therapeutic approach to highly-active antiretroviral therapy for the eradication of HIV. Our novel histone deacetylase inhibitor NCH-51 induced expression of latent HIV-1 with minimal cytotoxicity. Using chromatin immunoprecipitation assays, we observed a reduction of HDAC1 occupancy, histone hyperacetylation and the recruitment of positive transcription factors at the HIV-1 promoter in latently infected-cells under the treatment with NCH-51. Mutation studies of the long terminal repeat (LTR) revealed NCH-51 mediated gene expression through the Sp1 sites. When Sp1 expression was knocked-down by small interfering RNA, the NCH-51-mediated activation of a stably integrated HIV-1 LTR was attenuated. Moreover, the Sp1 inhibitor mithramycin A abolished the effects of NCH-51.
authors.affiliation: Department of Molecular and Cellular Biology, Nagoya City University Graduate School for Medical Sciences, Nagoya, Aichi, Japan.
authors.forename: Ann Florence B
authors.initials: AF
authors.lastname: Victoriano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Imai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Togami
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ueno
authors.forename: Kaori
authors.initials: K
authors.lastname: Asamitsu
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Ochiai
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D000107:Acetylation / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000172:deficiency / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D020079:Terminal Repeat Sequences / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects* / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; C524831:NCH-51 compound; D009707:Nucleosomes; D016329:Sp1 Transcription Factor; D013438:Sulfhydryl Compounds; D006655:Histone Deacetylases