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J. Virol. doi:10.1128/JVI.00893-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Dendritic cells infected with human immunodeficiency virus type 1 (HIV-1) vpr(+) virus induce CD8⁺ T cell apoptosis via upregulation of TNF alpha

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

^* To whom correspondence should be addressed. Email: velpandi{at}pitt.edu.

	Abstract

HIV-1 viral protein R (Vpr) plays a crucial role in viral replication and pathogenesis by inducing cell cycle arrest, apoptosis, translocation of pre integration complex (PIC), potentiation of glucocorticoid action, impairment of dendritic cell (DC) maturation and T cell activation. Recent studies involving the direct effect of Vpr on DC and T cells indicated that HIV-1 virus containing Vpr selectively impairs phenotypic maturation, cytokine network and antigen presentation in DC and dysregulated co-stimulatory molecules and cytokine production in T cells. Here we have further investigated the indirect effect of HIV-1 vpr(+) virus infected DC on bystander CD8⁺ T cell population. Our results indicate that HIV-1 vpr(+) virus infected DC dysregulated CD8+ T cell proliferation and induced apoptosis. Vpr containing virus infected DC-mediated CD8⁺ T cell killing occurred in part through enhanced TNF-alpha production by infected DC, and subsequent induction of death receptor signaling and activation of 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.

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]