Involvement of Sp1 in Butyric Acid-Induced HIV-1 Gene Expression
Involvement of Sp1 in Butyric Acid-Induced HIV-1 Gene Expression
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DOI：
10.1159/000430213
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发表时间：
2015-09-01
影响因子：
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通讯作者：
Ochiai, Kuniyasu
中科院分区：
文献类型：
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作者：
Imai, Kenichi;Okamoto, Takashi;Ochiai, Kuniyasu
背景/目标：人类免疫缺陷病毒-1（HIV-1）建立潜伏感染及其再激活的能力被认为是HIV-1感染进展的关键。我们以前报道，细菌代谢产物丁酸，作为一个有效的抑制剂组蛋白脱乙酰酶（HDAC），可以导致诱导HIV-1的转录，但是，分子机制仍不清楚。本研究的目的是研究丁酸对HIV-1基因表达的影响。方法：采用荧光素酶法和染色质免疫沉淀法检测丁酸介导的HIV-1基因表达。采用Western blot和丽莎检测HIV-1。结果：我们发现HIV-1启动子内的Sp1结合位点主要参与丁酸介导的HIV-1激活。事实上，小干扰RNA和Sp1抑制剂光神霉素A的Sp1敲低消除了丁酸的作用。我们还观察到cAMP反应元件结合蛋白（CBP）是丁酸诱导的HIV-1活化所必需的。结论：这些结果表明，丁酸通过抑制Sp1相关的HDAC活性和将CBP募集到HIV-1 LTR来刺激HIV-1启动子。我们的研究结果表明，Sp1应被视为抗病毒治疗的治疗靶点之一，对HIV-1感染的丁酸产生菌加重。版权所有（C）2015 S. Karger AG，巴塞尔
Background/Aims: The ability of human immunodeficiency virus-1(HIV-1) to establish latent infection and its re-activation is considered critical for progression of HIV-1 infection. We previously reported that a bacterial metabolite butyric acid, acting as a potent inhibitor of histone deacetylases (HDACs), could lead to induction of HIV-1 transcription; however, the molecular mechanism remains unclear. The aim of this study was to investigate the effect of butyric acid on HIV-1 gene expression. Methods: Butyric acid-mediated HIV-1 gene expression was determined by luciferase assay and Chromatin immunoprecipitation assay. Western blot analysis and [LISA were used for the detection of HIV-1. Results: We found that Sp1 binding sites within the HIV-1 promoter are primarily involved in butyric acid-mediated HIV-1 activation. In fact, Sp1 knockdown by small interfering RNA and the Sp1 inhibitor mithramycin A abolished the effect of butyric acid. We also observed that cAMP response element-bindingbinding protein (CBP) was required for butyric acid-induced HIV-1 activation. Conclusions: These results suggest that butyric acid stimulates HIV-1 promoter through inhibition of the Sp1-associated HDAC activity and recruitment of CBP to the HIV-1 LTR. Our findings suggest that Sp1 should be considered as one of therapeutic targets in anti-viral therapy against HIV-1 infection aggravated by butyric acid-producing bacteria. Copyright (C) 2015 S. Karger AG, Basel