title: HIV-1 viral protein R compromises cellular immune function in vivo.
abstract: 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 T(h)1 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 T(h)2 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.
authors.affiliation: Department of Infectious Diseases & Microbiology, University of Pittsburgh, PA 15261, USA.
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: Sagar
authors.initials: S
authors.lastname: Kudchodkar
authors.forename: Donghui
authors.initials: D
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Ramanathan
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Dayes
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D007114:Immunization; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D016336:Gene Products, vpr; D015483:HIV Antibodies; D007371:Interferon-gamma