HSP70 binding protein 1 (HspBP1) suppresses HIV-1 replication by inhibiting NF-κB mediated activation of viral gene expression

Priyanka Chaudhary, Sohrab Zafar Khan, Pratima Rawat, Tracy Augustine, Deborah A. Raynes, Vince Guerriero, Debashis Mitra

    Research output: Contribution to journalArticlepeer-review

    22 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)1613-1629
    Number of pages17
    JournalNucleic acids research
    Volume44
    Issue number4
    DOIs
    StatePublished - Oct 19 2015

    ASJC Scopus subject areas

    • Genetics

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