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, Vincent Guerriero, Debashis Mitra

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

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Viral Genes
HIV-1
Carrier Proteins
Gene Expression
HIV Long Terminal Repeat
HSP40 Heat-Shock Proteins
Virus Activation
HSP70 Heat-Shock Proteins
Terminal Repeat Sequences
Chromatin Immunoprecipitation
Transcriptional Activation
HIV Infections
Gels
Binding Sites
Viruses

ASJC Scopus subject areas

  • Genetics

Cite this

HSP70 binding protein 1 (HspBP1) suppresses HIV-1 replication by inhibiting NF-κB mediated activation of viral gene expression. / Chaudhary, Priyanka; Khan, Sohrab Zafar; Rawat, Pratima; Augustine, Tracy; Raynes, Deborah A.; Guerriero, Vincent; Mitra, Debashis.

In: Nucleic Acids Research, Vol. 44, No. 4, 19.10.2015, p. 1613-1629.

Research output: Contribution to journalArticle

Chaudhary, Priyanka ; Khan, Sohrab Zafar ; Rawat, Pratima ; Augustine, Tracy ; Raynes, Deborah A. ; Guerriero, Vincent ; Mitra, Debashis. / HSP70 binding protein 1 (HspBP1) suppresses HIV-1 replication by inhibiting NF-κB mediated activation of viral gene expression. In: Nucleic Acids Research. 2015 ; Vol. 44, No. 4. pp. 1613-1629.
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