title: HSP70 binding protein 1 (HspBP1) suppresses HIV-1 replication by inhibiting NF-κB mediated activation of viral gene expression.
abstract: HIV-1 efficiently hijacks host cellular machinery and exploits a plethora of host-viral interactions for its successful survival. Identifying host factors that affect susceptibility or resistance to HIV-1 may offer a promising therapeutic strategy against HIV-1. Previously, we have reported that heat shock proteins, HSP40 and HSP70 reciprocally regulate HIV-1 gene-expression and replication. In the present study, we have identified HSP70 binding protein 1 (HspBP1) as a host-intrinsic inhibitor of HIV-1. HspBP1 level was found to be significantly down modulated during HIV-1 infection and virus production inversely co-related with HspBP1 expression. Our results further demonstrate that HspBP1 inhibits HIV-1 long terminal repeat (LTR) promoter activity. Gel shift and chromatin immunoprecipitation assays revealed that HspBP1 was recruited on HIV-1 LTR at NF-κB enhancer region (κB sites). The binding of HspBP1 to κB sites obliterates the binding of NF-κB hetero-dimer (p50/p65) to the same region, leading to repression in NF-κB mediated activation of LTR-driven gene-expression. HspBP1 also plays an inhibitory role in the reactivation of latently infected cells, corroborating its repressive effect on NF-κB pathway. Thus, our results clearly show that HspBP1 acts as an endogenous negative regulator of HIV-1 gene-expression and replication by suppressing NF-κB-mediated activation of viral transcription.
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra 411007, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Chaudhary
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra 411007, India.
authors.forename: Sohrab Zafar
authors.initials: SZ
authors.lastname: Khan
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra 411007, India.
authors.forename: Pratima
authors.initials: P
authors.lastname: Rawat
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra 411007, India.
authors.forename: Tracy
authors.initials: T
authors.lastname: Augustine
authors.affiliation: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Raynes
authors.affiliation: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Vince
authors.initials: V
authors.lastname: Guerriero
authors.affiliation: National Centre for Cell Science, Pune, Maharashtra 411007, India dmitra@nccs.res.in dmitra01@yahoo.co.in.
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000235:genetics*; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018840:HSP70 Heat-Shock Proteins; C116331:HSPBP1 protein, human; D016328:NF-kappa B