Molecular Therapy
Volume 12, Issue 5, November 2005, Pages 910-921
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Article
HIV-1 Viral Protein-R (VPR) Protects against Lethal Superantigen Challenge While Maintaining Homeostatic T Cell Levels in Vivo

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Abstract

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-κB. In this regard we sought to test its effects in vivo on an NF-κB-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.

Keywords

HIV-1 Vpr
NF-κB
T cell activation
staphylococcal endotoxin B
cytokine
sepsis
glucocorticoid receptor

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