title: Involvement of Sp1 in butyric acid-induced HIV-1 gene expression.
abstract: OBJECTIVE
  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 ELISA 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-binding-binding 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.
authors.affiliation: Department of Microbiology, Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Imai
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Ochiai
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D012367:RNA, Viral; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D020148:Butyric Acid; C066851:mithramycin A; D008926:Plicamycin