INFECTION & IMMUNE RESPONSES TO A? HUMAN RETROVIRUS XMRV IN MACAQUES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The aims of this protocol are to document whether the human XMR virus is able to replicate in a model close to man, i.e. rhesus macaque. If XMRV is able to induce an active infection, what are the viral kinetics, dissemination and antiviral immune responses in this model. A strong correlation has established between the infection with a newly identified gammaretrovirus related to MuLV in prostate tumors from patients exhibiting a genetic inactivation of the RNASEL pathway (R462Q) linked to type I IFN antiviral mechanism. Thus, the hypothesis is that infection with the XMR virus in patients with a deficiency in the RNASEL or potentially other select innate antiviral pathway may lead to or at least contribute to rise of prostate tumors, especially in younger patients. This has obvious health program consequences including the potential for transmission via blood transfusion. This exploratory project will attempt to set up an in vivo model as well as generate reagents for use as screening tools for ensuring the safety of the blood supply. We have shown that XMRV induces a persistent clinically silent infection in rhesus macaques with very low viremia that may be reactivated following immunization/immune activation. Evidence for viral replication was also seen during the chronic phase in most reproductive organs and lymphoid tissues, suggesting likely transmission via sexual contact. This will be tested in new animals thanks to a new source of funding as well as the role of XMRV in the prostate in which early infection appears enriched.