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Journal of Virology, July 2005, p. 7990-8003, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.7990-8003.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Vpr Impairs Dendritic Cell Maturation and T-Cell Activation: Implications for Viral Immune Escape

Biswanath Majumder,1 Michelle L. Janket,1,{dagger} Elizabeth A. Schafer,1,{dagger} Keri Schaubert,2 Xiao-Li Huang,1 June Kan-Mitchell,2 Charles R. Rinaldo Jr.,1 and Velpandi Ayyavoo1*

Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261,1 Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 482012

Received 9 November 2004/ Accepted 7 March 2005

Antigen presentation and T-cell activation are dynamic processes involving signaling molecules present in both APCs and T cells. Effective APC function and T-cell activation can be compromised by viral immune evasion strategies, including those of human immunodeficiency virus type 1 (HIV-1). In this study, we determined the effects of HIV-1 Vpr on one of the initial target of the virus, dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8-specific T-cell stimulation function followed by a second signal. Vpr impaired the expression of CD80, CD83, and CD86 at the transcriptional level without altering normal cellular transcription. Cytokine profiling indicated that the presence of Vpr inhibited production of interleukin 12 (IL-12) and upregulated IL-10, whereas IL-6 and IL-1ß were unaltered. Furthermore, DC infected with HIV-1 vpr+ significantly reduced the activation of antigen-specific memory and recall cytotoxic-T-lymphocyte responses. Taken together, these results indicate that HIV-1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the maturation of costimulatory molecules and cytokines essential for immune activation.

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

{dagger} Both authors contributed equally to this work.

Journal of Virology, July 2005, p. 7990-8003, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.7990-8003.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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