RHESUS HHV8 HOMOLOGUE IN AIDS-RELATED MALIGNANCIES

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

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. This project is a continuation of my NIH RO1 (1997), which supports the investigation of rhesus macaque rhadinovirus (RRV) infection and pathogenesis in rhesus macaques (RM), as a model for better understanding Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) pathogenesis in humans. My laboratory has shown that the simian immunodeficiency virus (SIV)/RRV/RM animal model recapitulates many of the lymphoproliferative disorders that KSHV is capable of inducing in AIDS patients. These include multicentric Castleman's disease, non-Hodgkin's lymphoma and retroperitoneal fibromatosis, a proliferative mesenchymal lesion that possesses cellular features that resemble Kaposi sarcoma. During the last year, my laboratory has focused on elucidating the cell types RRV infects in vivo, and which viral gene products may play a role in the maintenance of infection and disease progression. Our more recent findings indicate that the viral interferon regulatory factors (vIRFs) play a significant role in attenuating the innate immune response, allowing the virus to establish a robust infection, which leads to viral persistence. Additionally, we constructed another recombinant RRV that is incapable of directing the synthesis of the viral CD200 homologue, a novel viral immune regulatory protein. The vCD200 protein is thought to interact with the CD200 receptor found on monocytes/macrophages to down regulate inflammation and activation. The recombinant RRV vCD200ns replicates well in vitro and in vivo, and produces higher viral loads compared to wild type BAC-derived virus. Future studies will focus on the host immune response to vCD200ns virus infection and how this impacts viral loads.