title: Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways.
abstract: Human immunodeficiency virus-1 (HIV-1) infection leads to changes in cellular gene expression, which in turn tend to modulate viral gene expression and replication. Cellular heat shock proteins (HSPs) are induced upon heat shock, UV irradiation and microbial or viral infections. We have reported earlier Nef-dependent induction of HSP40 leading to increased HIV-1 gene expression; however, the mechanism of induction remained to be elucidated. As expression of HSPs is regulated by heat shock factors (HSFs), we have now studied the role of HSF1 not only in Nef-dependent HSP40 induction but also in HIV-1 gene expression. Our results show that HSF1 is also induced during HIV-1 infection and it positively regulates HIV-1 gene expression by two distinct pathways. First, along with Nef it activates HSP40 promoter which in turn leads to increased HIV-1 gene expression. Second, HSF1 directly interacts with newly identified HSF1 binding sequence on HIV-1 LTR promoter and induces viral gene expression and replication. Thus, the present work not only identifies a molecular basis for HSF1-mediated enhancement of viral replication but also provides another example of how HIV-1 uses host cell machinery for its successful replication in the host.
authors: National Centre for Cell Science, Ganeshkhind, Pune 411 007, India.
authors: Pratima
authors: P
authors: Rawat
authors: Debashis
authors: D
authors: Mitra
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D050956:HSP40 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1