HIV-1 Viral protein-r (Vpr) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo.
The HIV-1 accessory protein Vpr exhibits many interesting features related to macrophage and T cell biology. As a viral protein or as a soluble molecule it can suppress immune cell activation and cytokine production in vitro in part by targeted inhibition of NF-kappaB. In this regard we sought to test its effects in vivo on an NF-kappaB-dependent immune pathway. We examined the activity of Vpr in a lethal toxin-mediated challenge model in mice. Intravenous delivery of Vpr was sufficient to protect mice from lethal challenge with staphylococcal endotoxin B (SEB). Furthermore, Vpr protected host CD4+ T cells from in vivo depletion likely by preventing induction of AICD of SEB-exposed cells in a post-toxin-binding fashion. Understanding the biology of Vpr's activities in this model may allow for new insight into potential mechanisms of hyperinflammatory disease and into Vpr pathobiology in the context of HIV infection.
Muthumani
Karuppiah
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 505 Stellar Chance Building, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Choo
Andrew Y
AY
Hwang
Daniel S
DS
Dayes
Nathanael S
NS
Chattergoon
Michael
M
Mayilvahanan
Shanmugam
S
Thieu
Khanh P
KP
Buckley
Peter T
PT
Emmanuel
Joann
J
Premkumar
Arumugam
A
Weiner
David B
DB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D016336:Gene Products, vpr / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D066298:In Vitro Techniques; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology*; D013210:Staphylococcus; D013601:T-Lymphocytes / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D004731:Endotoxins; D016336:Gene Products, vpr; D016328:NF-kappa B; D054325:vpr Gene Products, Human Immunodeficiency Virus