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Journal of Virology, July 2007, p. 7388-7399, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00893-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha{triangledown}

Biswanath Majumder, Narasimhan J. Venkatachari, Elizabeth A. Schafer, Michelle L. Janket, and Velpandi Ayyavoo*

Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261

Received 2 May 2006/ Accepted 23 April 2007

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) plays a crucial role in viral replication and pathogenesis by inducing cell cycle arrest, apoptosis, translocation of preintegration complex, potentiation of glucocorticoid action, impairment of dendritic cell (DC) maturation, and T-cell activation. Recent studies involving the direct effects of Vpr on DCs and T cells indicated that HIV-1 containing Vpr selectively impairs phenotypic maturation, cytokine network, and antigen presentation in DCs and dysregulates costimulatory molecules and cytokine production in T cells. Here, we have further investigated the indirect effect of HIV-1 Vpr+ virus-infected DCs on the bystander CD8+ T-cell population. Our results indicate that HIV-1 Vpr+ virus-infected DCs dysregulate CD8+ T-cell proliferation and induce apoptosis. Vpr-containing virus-infected DC-mediated CD8+ T-cell killing occurred in part through enhanced tumor necrosis factor alpha production by infected DCs and subsequent induction of death receptor signaling and activation of the caspase 8-dependent pathway in CD8+ T cells. Collectively, these results provide evidence that Vpr could be one of the important contributors to the host immune escape by HIV-1 through its ability to dysregulate both directly and indirectly the DC biology and T-cell functions.

* Corresponding author. Mailing address: Department of Infectious Diseases and Microbiology, University of Pittsburgh, GSPH, 130 Desoto Street, Pittsburgh, PA 15261. Phone: (412) 624-3070. Fax: (412) 624-5612. E-mail: velpandi{at}pitt.edu

{triangledown} Published ahead of print on 2 May 2007.

Journal of Virology, July 2007, p. 7388-7399, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00893-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Majumder, B., Venkatachari, N. J., O'Leary, S., Ayyavoo, V. (2008). Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells. J. Virol. 82: 7189-7200 [Abstract] [Full Text]  


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