RHESUS HHV8 HOMOLOGUE IN AIDS-RELATED MALIGNANCIES

艾滋病相关恶性肿瘤中的恒河猴 HHV8 同源物

• 批准号: 8357730
• 负责人: SCOTT W WONG
• 金额: $ 24.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357730
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Animal Model; Attenuated; CD 200; Disease Progression; Fibromatoses; Funding; Future; Grant; Homologous Gene; Human; Human Herpesvirus 8; Immune; Immune response; In Vitro; Infection; Inflammation; Investigation; Kaposi Sarcoma; Laboratories; Lesion; Lymphoproliferative Disorders; Macaca mulatta; Maintenance; Mesenchymal; Modeling; Multicentric Angiofollicular Lymphoid Hyperplasia; National Center for Research Resources; Non-Hodgkin' s Lymphoma; Pathogenesis; Patients; Play; Primates; Principal Investigator; Proteins; Recombinants; Research; Research Infrastructure; Resources; Retroperitoneal Space; Rhadinovirus; Role; SIV; Source; United States National Institutes of Health; Viral; Viral Load result; Viral Proteins; Virus; Virus Diseases; cell type; cost; genetic regulatory protein; in vivo; macrophage; monocyte; novel; receptor; viral interferon regulatory factor

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目是我的NIH RO 1（1997）的延续，该项目支持研究恒河猴（RM）中恒河猴鼻状病毒（RRV）的感染和发病机制，作为更好地了解卡波西肉瘤相关疱疹病毒（KSHV）/人类疱疹病毒8（HHV 8）在人类中发病机制的模型。我的实验室已经表明，猴免疫缺陷病毒（SIV）/RRV/RM动物模型重现了KSHV能够在AIDS患者中诱导的许多淋巴组织增生性疾病。这些包括多中心Castleman病，非霍奇金淋巴瘤和腹膜后纤维瘤病，一种具有类似卡波西肉瘤细胞特征的增生性间质病变。 在过去的一年里，我的实验室一直致力于阐明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。我们最近的研究结果表明，病毒干扰素调节因子（vIRF）在减弱先天性免疫应答中发挥重要作用，使病毒能够建立强大的感染，从而导致病毒持续存在。此外，我们构建了另一种重组RRV，它不能指导病毒CD 200同源物的合成，这是一种新的病毒免疫调节蛋白。vCD 200蛋白被认为与单核细胞/巨噬细胞上发现的CD 200受体相互作用，以下调炎症和活化。重组RRV vCD 200 ns在体外和体内复制良好，与野生型BAC衍生病毒相比，产生更高的病毒载量。未来的研究将集中在宿主对vCD 200 ns病毒感染的免疫反应以及这如何影响病毒载量。