The HIV-1 accessory gene vpr can inhibit antigen-specific immune function.
The 14-kDa HIV-1 accessory gene vpr has been reported to have effects on host cell biology. These activities include inhibition of cell proliferation, inhibition of NF-kappaB activation, inhibition of CD4 T-cell proliferation, and induction of apoptosis in tissue culture. This collection of activities could, in theory, impact host cell immune responses. We tested the activity of recombinant Vpr protein to inhibit T-cell activation in vitro. Here, we present data illustrating that the Vpr protein can significantly suppress T-cell activation-related cytokine elaboration and proliferation. In vivo, we observed that covaccination with plasmids expressing the vpr gene product profoundly reduces antigen-specific CD8-mediated cytotoxic T lymphocyte (CTL) activity. This supports that vpr might compromise T-cell immunity in vivo during infection. To study this aspect of Vpr biology, we developed an Adenoviral Vpr expression vector for delivery of Vpr to immune cells and to study Vpr function in the absence of other lentiviral gene products. This vector delivers a functional Vpr protein to immune cells including antigen-presenting cells (APCs). We observe that the Adeno-Vpr vector suppresses human CD4 T-cell proliferation driven by immune activation in vitro. Further study of the biology of Vpr will likely have importance for a clearer understanding of host pathogenesis as well as have important implications for HIV vaccine development.
Muthumani
Karuppiah
K
University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Hwang
Daniel S
DS
Dayes
Nathaniel S
NS
Kim
J Joseph
JJ
Weiner
David B
DB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016334:Genes, vpr; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016827:CD8 Antigens; D016207:Cytokines