HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo

Karuppiah Muthumani, Andrew Y. Choo, Daniel S. Hwang, Nathanael S. Dayes, Michael Chattergoon, Shanmugam Mayilvahanan, Khanh P. Thieu, Peter T. Buckley, Joann Emmanuel, Arumugam Premkumar, David B. Weiner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)910-921
Number of pages12
JournalMolecular Therapy
Volume12
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Keywords

  • Cytokine
  • Glucocorticoid receptor
  • HIV-1 Vpr
  • NF-κB
  • Sepsis
  • Staphylococcal endotoxin B
  • T cell activation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo'. Together they form a unique fingerprint.

Cite this