title: Inhibition of NF-κB activity by HIV-1 Vpr is dependent on Vpr binding protein.
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 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.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kogan
authors.forename: Satish
authors.initials: S
authors.lastname: Deshmane
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gracely
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
mesh_terms: D002352:Carrier Proteins; D002478:Cells, Cultured; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D055551:HSP27 Heat-Shock Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000072000:NF-KappaB Inhibitor alpha