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

基本信息

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
项目类别：
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&apos 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

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&apos 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

展开

项目摘要

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.

该副本是利用资源的众多研究子项目之一由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持而且，副投影的主要研究员可能是其他来源提供的包括其他NIH来源。列出的总费用可能代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。该项目是我的NIH RO1（1997）的延续，该项目支持猕猴赤道rhadinovirus（RRV）感染和发病机理的调查，以更好地了解Kaposi Sarcoma sarcoma sarcoma Issp.我的实验室表明，Simian免疫缺陷病毒（SIV）/RRV/RM动物模型概括了KSHV能够诱导艾滋病患者的许多淋巴增生性疾病。其中包括多中心骑员疾病，非霍奇金的淋巴瘤和腹膜后纤维瘤病，这是一种具有类似Kaposi肉瘤的细胞特征的增殖性间充质病变。在过去的一年中，我的实验室重点是阐明体内RRV感染的细胞类型，哪种病毒基因产物可能在维持感染和疾病进展中起作用。我们最近的发现表明，病毒干扰素调节因子（VIRF）在减轻先天免疫反应中起着重要作用，从而使病毒能够建立强大的感染，从而导致病毒持久性。此外，我们构建了另一个重组RRV，该RRV无法指导病毒CD200同源物的合成，这是一种新型的病毒免疫调节蛋白。 VCD200蛋白被认为与在单核细胞/巨噬细胞上发现的CD200受体相互作用，以降低调节炎症和激活。重组RRV VCD200NS在体外和体内复制很好，与野生型BAC衍生的病毒相比，病毒载量更高。未来的研究将集中于宿主对VCD200NS病毒感染的免疫反应以及这如何影响病毒载荷。