JOURNAL ARTICLE

Novel histone deacetylase inhibitor NCH-51 activates latent HIV-1 gene expression

Ann Florence B Victoriano, Kenichi Imai, Hiroaki Togami, Takaharu Ueno, Kaori Asamitsu, Takayoshi Suzuki, Naoki Miyata, Kuniyasu Ochiai, Takashi Okamoto
FEBS Letters 2011 April 6, 585 (7): 1103-11
21402072
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.

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