HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo Journal Article
| Authors: | Muthumani, K.; Choo, A. Y.; Hwang, D. S.; Dayes, N. S.; Chattergoon, M.; Mayilvahanan, S.; Thieu, K. P.; Buckley, P. T.; Emmanuel, J.; Premkumar, A.; Weiner, D. B. |
| Article Title: | HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo |
| 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. Copyright © The American Society of Gene Therapy. |
| Keywords: | signal transduction; controlled study; pathogenesis; nonhuman; human immunodeficiency virus infection; protein function; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; liver toxicity; protein targeting; animal experiment; animal model; immunoglobulin enhancer binding protein; in vivo study; in vitro study; mice, inbred balb c; animalia; cytokine; liver; lymphocyte activation; cytokines; shock; nf-kappa b; cd4-positive t-lymphocytes; sepsis; cytokine production; immunomodulation; human immunodeficiency virus; macrophage; homeostasis; lymphocyte count; human immunodeficiency virus 1; hiv-1; glucocorticoid receptor; nf-κb; t cell activation; endotoxin; superantigen; staphylococcus; vpr protein; gene products, vpr; hiv-1 vpr; staphylococcal endotoxin b; endotoxins |
| Journal Title: | Molecular Therapy |
| Volume: | 12 |
| Issue: | 5 |
| ISSN: | 1525-0016 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-11-01 |
| Start Page: | 910 |
| End Page: | 921 |
| Language: | English |
| DOI: | 10.1016/j.ymthe.2005.05.009 |
| PUBMED: | 16006193 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 24 October 2012" - "CODEN: MTOHC" - "Source: Scopus" |
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