Journal
FEBS LETTERS
Volume 585, Issue 7, Pages 1103-1111Publisher
WILEY
DOI: 10.1016/j.febslet.2011.03.017
Keywords
HIV-1; Viral latency; Histone deacetylase; Histone deacetylase inhibitor; Chromatin remodeling; HIV transcription
Funding
- Ministry of Health, Labor and Welfare
- Japanese Health Sciences Foundation
- Grants-in-Aid for Scientific Research [23592714, 20390034] Funding Source: KAKEN
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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. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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