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International Immunology, Vol. 14, No. 1, 13-22, January 2002
© 2002 Japanese Society for Immunology

HIV-1 viral protein R compromises cellular immune function in vivo

Velpandi Ayyavoo1, Karuppiah Muthumani, Sagar Kudchodkar, Donghui Zhang, P. Ramanathan, Nathanael S. Dayes, J. J. Kim, Jeong-Im Sin, Luis J. Montaner2 and David B. Weiner

Department of Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA
1 Department of Infectious Diseases & Microbiology, University of Pittsburgh, PA 15261, USA
2 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA

Correspondence to: D. B. Weiner

HIV-1 viral protein R (Vpr) is a virion-associated gene product that profoundly affects T cell proliferation, induces apoptosis and can affect cytokine production in part through interfering with NF-{kappa}B-mediated transcription from host cells. Collectively, these effects support that Vpr could influence immune activation in vivo. However, this effect of Vpr has not been explored previously. Here we examined the effect of Vpr expression in an in vivo model system on the induction of antigen-specific immune responses using a DNA vaccine model. Vpr co-vaccination significantly altered the immune response to co-delivered antigen. Specifically, in the presence of Vpr, inflammation was markedly reduced compared to antigen alone. Vpr reduced antigen-specific CD8-mediated cytotoxic T lymphocyte activity and suppressed Th1 immune responses in vivo as evidenced by lower levels of IFN-{gamma}. In the presence of Vpr, there is a profound shift in isotype towards a Th2 response as determined by the IgG2a:IgG1 ratio. The data support that Vpr compromises antigen-specific immune responses and ultimately effector cell function, thus confirming a strong selective advantage to the virus at the expense of the host.

Keywords: antigen-presenting cell, antigen-specific immune response, HIV-1 viral protein R, T cell activation, Th1/Th2 cytokine, vaccination

Transmitting editor: D. R. Green


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