Herpesvirus latency and reactivation in macaque models of human disease

人类疾病猕猴模型中疱疹病毒的潜伏期和重新激活

基本信息

批准号：
7924743
负责人：
TIMOTHY M ROSE
金额：
$ 60.95万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-07 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924743
关键词：
Acute Affect Animal Model Animals Antibodies Antibody Formation Antigens Bioinformatics Biological Assay Biology Biomedical Research Cells Cessation of life Cloning Communities Cyclosporine Data Development Disease Evaluation Family suidae Fibromatoses Funding Future Genes Genetic Genome Genomics Glycoproteins Grant Herpesviridae Homologous Gene Human Human Herpesvirus 8 Immune Sera Immune response Immune system Immunosuppression Immunosuppressive Agents Infection Kaposi Sarcoma Knowledge Libraries Life Cycle Stages Lymphoma Lytic Macaca Macaca mulatta Malignant Neoplasms Modeling Molecular Monoclonal Antibodies Monoclonal Antibody R24 Multicentric Angiofollicular Lymphoid Hyperplasia Names Pathogenicity Pharmaceutical Preparations Play Population Prevalence Primates Proteins Protocols documentation Reagent Recombinant Proteins Research Resources Retroperitoneal Space Rhadinovirus Role SIV Sequence Analysis Serological Staging Tail Viral Viral Pathogenesis Viral Proteins Virion Virus Washington animal model development base human disease in vivo insight latency-associated nuclear antigen latent infection lytic replication member neoplastic cell prototype reactivation from latency research study tool transmission process

项目摘要

DESCRIPTION (provided by applicant): This resource-related (R24) grant proposes to characterize the two distinct lineages of macaque rhadinovirus related to human herpesvirus 8 (HHV8), RV1 and RV2. New reagents and assays have been developed to study the latency and reactivation of these viruses in macaque models of human disease. Our proposed studies initially focus on the rhadinoviruses of the pig-tailed macaque, the most common macaque species maintained at the Washington National Primate Research Center. The macaque rhadinoviruses are highly prevalent in captive macaque populations and express viral proteins that interact with host cellular proteins, including those affecting the host immune system. Thus, the presence of these viruses may complicate and/or confound the interpretation of data from macaque models of human disease. The potential for interference may be most acute in macaque models of immunosuppression. Both RV1 and RV2 have been associated with significant diseases in macaques that closely resemble cancers associated with HHV8 in humans, including Kaposi sarcoma (KS), lymphoma and multicentric Castleman's disease. Thus, the characterization of the macaque rhadinoviruses, including the development of specific reagents and assays that enable the evaluation of their biology and life cycles, is an important prerequisite for the development of herpesvirus-related macaque models and to the successful use of macaques as models of other diseases. Specifically, we propose to 1) Complete the genomic sequence of the macaque RV1 rhadinovirus, RFHVMn, 2) Develop specific assays to study the infection and prevalence of the macaque RV1 and RV2rhadinoviruses, 3) Characterize the experimental infection of naive macaques with RV1 and RV2rhadinoviruses in vivo, and 4) Characterize the reactivation of existing latent infections of RV1 and RV2rhadinoviruses in macaques by treatment with immunosuppressive agents.

描述（由申请人提供）：此与资源相关的（R24）赠款提出了表征与人类疱疹病毒8（HHV8），RV1和RV2相关的猕猴rhadinovirus的两个不同谱系。已经开发了新的试剂和测定，以研究人类疾病猕猴模型中这些病毒的潜伏期和重新激活。我们提出的研究最初着重于猪尾猕猴的犀牛病毒，这是华盛顿国家灵长类动物研究中心维持的最常见的猕猴。猕猴的鼻虫病毒在圈养的猕猴种群中非常普遍，并且与宿主细胞蛋白相互作用，包括影响宿主免疫系统的病毒蛋白。因此，这些病毒的存在可能会使人类疾病猕猴模型的数据的解释复杂化和/或混淆。在免疫抑制的猕猴模型中，干扰的潜力可能是最急性的。 RV1和RV2都与猕猴的重大疾病有关，这些疾病与人类中与HHV8相关的癌症非常相似，包括Kaposi肉瘤（KS），淋巴瘤和多中心骑士氏病。因此，猕猴的菱形病毒的表征，包括开发特定试剂和能够评估其生物学和生命周期的测定方法，是开发与疱疹病毒相关的猕猴模型以及成功将猕猴用作其他疾病的模型的重要先决条件。 Specifically, we propose to 1) Complete the genomic sequence of the macaque RV1 rhadinovirus, RFHVMn, 2) Develop specific assays to study the infection and prevalence of the macaque RV1 and RV2rhadinoviruses, 3) Characterize the experimental infection of naive macaques with RV1 and RV2rhadinoviruses in vivo, and 4) Characterize the reactivation通过用免疫抑制剂治疗猕猴中RV1和RV2RHADINOVIRES的现有潜在感染。