RHESUS HHV8 HOMOLOGUE IN AIDS-RELATED MALIGNANCIES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 本项目是My NIH RO1(1997)的延续，My NIH RO1支持恒河猴RRV感染及其在恒河猴(RM)中的发病机制的研究，作为更好地了解人类卡波西肉瘤相关疱疹病毒(KSHV)/人类疱疹病毒8型(HHV8)发病机制的模型。我的实验室已经证明，猴免疫缺陷病毒(SIV)/RRV/RM动物模型重现了KSHV能够在艾滋病患者中诱导的许多淋巴增殖性疾病。这些疾病包括多中心性Castleman病、非霍奇金淋巴瘤和腹膜后纤维瘤病，这是一种增生性间质病变，具有类似卡波西肉瘤的细胞特征。在过去的一年里，我的实验室专注于阐明RRV在体内感染的细胞类型，以及哪些病毒基因产物可能在维持感染和疾病进展中发挥作用。我们最近的发现表明，病毒干扰素调节因子(VIRFs)在减弱先天性免疫反应方面发挥着重要作用，使病毒能够建立强大的感染，从而导致病毒持续存在。此外，我们构建了另一个不能指导病毒CD200同源物的合成的重组RRV，CD200是一种新的病毒免疫调节蛋白。VCD200蛋白被认为与单核/巨噬细胞上发现的CD200受体相互作用，下调炎症和激活。重组RRV vCD200 ns在体外和体内复制良好，与野生型BAC来源的病毒相比，产生更高的病毒载量。未来的研究将集中在宿主对vCD200 ns病毒感染的免疫反应以及这如何影响病毒载量。

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.