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

doi:10.1016/j.ymthe.2005.05.009

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 journal › Article › peer-review

7 Scopus citations

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 language	English (US)
Pages (from-to)	910-921
Number of pages	12
Journal	Molecular Therapy
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.ymthe.2005.05.009
State	Published - Nov 2005
Externally published	Yes

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

Access to Document

10.1016/j.ymthe.2005.05.009

Cite this

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. (2005). HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo. Molecular Therapy, 12(5), 910-921. https://doi.org/10.1016/j.ymthe.2005.05.009

@article{4ca27ea6b9a94b19a2daa18b38f9ff3a,

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.",

keywords = "Cytokine, Glucocorticoid receptor, HIV-1 Vpr, NF-κB, Sepsis, Staphylococcal endotoxin B, T cell activation",

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

note = "Funding Information: We thank Michael J. Merva for administrative assistance and Dan Martinez and The Children's Hospital of Philadelphia–Abramson Research Center, Pathology Core Laboratories, for the liver hepatotoxicity study. Support from the NIH AIDS Research and Reference Reagents program and CFAR, University of Pennsylvania, is also acknowledged. This work was supported by grants from the NIH to D.B.W. and VGX Pharmaceuticals, Philadelphia, PA, to D.B.W. and K.M.",

year = "2005",

month = nov,

doi = "10.1016/j.ymthe.2005.05.009",

language = "English (US)",

volume = "12",

pages = "910--921",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - HIV-1 viral protein-R (VPR) protects against lethal superantigen challenge while maintaining homeostatic T cell levels in vivo

AU - Muthumani, Karuppiah

AU - Choo, Andrew Y.

AU - Hwang, Daniel S.

AU - Dayes, Nathanael S.

AU - Chattergoon, Michael

AU - Mayilvahanan, Shanmugam

AU - Thieu, Khanh P.

AU - Buckley, Peter T.

AU - Emmanuel, Joann

AU - Premkumar, Arumugam

AU - Weiner, David B.

N1 - Funding Information: We thank Michael J. Merva for administrative assistance and Dan Martinez and The Children's Hospital of Philadelphia–Abramson Research Center, Pathology Core Laboratories, for the liver hepatotoxicity study. Support from the NIH AIDS Research and Reference Reagents program and CFAR, University of Pennsylvania, is also acknowledged. This work was supported by grants from the NIH to D.B.W. and VGX Pharmaceuticals, Philadelphia, PA, to D.B.W. and K.M.

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

KW - Cytokine

KW - Glucocorticoid receptor

KW - HIV-1 Vpr

KW - NF-κB

KW - Sepsis

KW - Staphylococcal endotoxin B

KW - T cell activation

UR - http://www.scopus.com/inward/record.url?scp=27744440829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744440829&partnerID=8YFLogxK

U2 - 10.1016/j.ymthe.2005.05.009

DO - 10.1016/j.ymthe.2005.05.009

M3 - Article

C2 - 16006193

AN - SCOPUS:27744440829

SN - 1525-0016

VL - 12

SP - 910

EP - 921

JO - Molecular Therapy

JF - Molecular Therapy

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this