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Inhibition of NF-κB activity by HIV-1 Vpr is dependent on Vpr binding protein
Journal article   Open access   Peer reviewed

Inhibition of NF-κB activity by HIV-1 Vpr is dependent on Vpr binding protein

Michael Kogan, Satish Deshmane, Bassel Sawaya, Ed J Gracely, Kamel Khalili and Jay Rappaport
Journal of cellular physiology, v 228(4), pp 781-790
Apr 2013
PMID: 23001849
url
https://doi.org/10.1002/jcp.24226View
Published, Version of Record (VoR) Open

Abstract

Numerous studies have reported that Vpr alters NF-κB signaling in various cell types, however, the findings have been largely conflicting with reports of both stimulatory and inhibitory effects of Vpr. Our aim was to investigate the role of Vpr signaling in myeloid cells using an adenovirus based expression and indicator system. Our results show that Vpr is inhibitory to NF-κB, however, this effect is dependant on the particular manner of NF-κB stimulation. Consistent with this notion, we report that Vpr has inhibitory effects that are specific to the TNF-α pathway, but not affecting the LPS pathway, suggesting that differential targets of Vpr may exist for NF-κB regulation. Further, we identify VprBP as one possible cellular component of Vpr’s regulation of IκBα in response to TNF-α stimulation. We did not identify such a role for HSP27, which instead seems to inhibit Vpr functions. Chronically HIV-1 infected U1 cells with knockdown constructs for Vpr were unexpectedly less responsive to TNF-α mediated viral replication, perhaps suggesting that other HIV-1 components may antagonize these anti-NF-κB effects in infected cells. We hypothesize that Vpr may serve an important role in the context of viral infection and immune function in vivo, through its selective inhibition of NF-κB pathways.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Physiology
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