Conflict of Interest Statement: The authors have no conflicts of interests to declare.
Original Research Article
Inhibition of NF-κB activity by HIV-1 Vpr is dependent on Vpr binding protein†
Article first published online: 20 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 4, pages 781–790, April 2013
How to Cite
Kogan, M., Deshmane, S., Sawaya, B. E., Gracely, E. J., Khalili, K. and Rappaport, J. (2013), Inhibition of NF-κB activity by HIV-1 Vpr is dependent on Vpr binding protein. J. Cell. Physiol., 228: 781–790. doi: 10.1002/jcp.24226
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 21 SEP 2012 06:59AM EST
- Manuscript Accepted: 6 SEP 2012
- Manuscript Received: 28 JAN 2012
- NIH. Grant Numbers: RO1MH090910, 1T32MH079785
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 dependent 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. J. Cell. Physiol. 228: 781–790, 2013. © 2012 Wiley Periodicals, Inc.