GAMMA-2 HERPESVIRUS-ASSOCIATED JAPANESE MACAQUE ENCEPHALOMYELITIS

GAMMA-2 疱疹病毒相关日本猕猴脑脊髓炎

• 批准号: 8173262
• 负责人: SCOTT W WONG
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173262
• 关键词: Affect; Animals; Antibodies; Antiviral Response; Autoimmune Diseases; Bilateral; Blood specimen; Brain; Brain region; Chronic; Clinical; Computer Retrieval of Information on Scientific Projects Database; Demyelinations; Disease; Encephalomyelitis; Environmental Risk Factor; Exhibits; Funding; Genetic Predisposition to Disease; Grant; Human; Infection; Inflammation; Institution; Japanese Population; Lesion; Macaca; Magnetic Resonance Imaging; Modeling; Monitor; Multiple Sclerosis; Oregon; Paralysed; Pathology; Patients; Primates; Relapse; Research; Research Personnel; Resources; Rhadinovirus; Role; Sampling; Source; Spinal Cord; T-Lymphocyte; United States National Institutes of Health; Virus; Virus Diseases; astrogliosis; gamma-2 herpesvirus; gammaherpesvirus; genetic pedigree; nonhuman primate; novel; oculomotor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multiple sclerosis (MS) is an autoimmune disease of multifactorial origin hypothesized to involve virus infection, host genetic susceptibility and environmental factors. Of the viruses known to infect humans, the gamma-herpesviruses are considered to be the leading candidate, as MS patients have higher antibody titers to these viruses, and brain samples taken from MS patients possess virus specific T cells. In an effort to develop a nonhuman primate model of MS, we have characterized a novel encephalomyelitis that occurs spontaneously in a small percentage of animals in a colony of Japanese macaques (JM) at the Oregon National Primate Research Center. The disease, called Japanese macaque encephalomyelitis (JME), occurs in both progressive and relapsing-remitting forms and is characterized by brain and spinal cord demyelination that is accompanied by extensive astrogliosis. Affected animals develop debilitating motor and ocular disturbances. Approximately 10% of the animals in this colony appear to have chronic, subclinical lesions as evaluated by magnetic resonance imaging (MRI). Pedigree analysis indicates that particular lineages of animals are substantially more susceptible to this disease than others, suggesting a genetic predisposition to JME. In these studies, we investigated the role of a novel gamma-herpesvirus, referred to as Japanese macaque rhadinovirus (JMRV), isolated from the spinal cord from a JM that exhibited clinical signs consistent with JME. Four animals na¿ve for previous infection with JMRV were experimentally inoculated and monitored by MRI and blood sampling for alterations to the brain and induction of anti-viral responses. Two animals developed inflammation in the brain, with one animal developing bilateral paralysis. This animal was euthanized and found to exhibit axonal pathology consistent with MS. Furthermore, we have isolated JMRV from animals in this colony that is found within demyelinated JME lesions and not within unaffected regions of the brain.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 多发性硬化症（MS）是一种多因素来源的自身免疫性疾病，该疾病涉及病毒感染，宿主遗传易感性和环境因素。在已知感染人类的​​病毒中，伽马病毒被认为是领先的候选者，因为MS患者对这些病毒具有较高的抗体滴度，并且从MS患者中获取的大脑样本具有特定于病毒的T细胞。为了开发MS的非人类私人模型，我们表征了一种新型的脑脊髓炎，该脑炎在俄勒冈州国家灵长类动物研究中心的日本猕猴（JM）中发起了一小部分动物。该疾病被称为日本猕猴脑脊髓炎（JME），出现在进行性和复发形式中，其特征是大脑和脊髓脱髓鞘，这是通过广泛的星形胶质细胞增多而实现的。受影响的动物会导致运动和眼部障碍。通过磁共振成像（MRI）评估，这种菌落外观中约有10％的动物具有慢性亚临床病变。谱系分析表明，动物的特定谱系比其他疾病更容易受到这种疾病的影响，这表明对JME的遗传倾向。在这些研究中，我们调查了一种新型的γ-疱疹病毒，称为日本猕猴rhadinovirus（JMRV），该病毒是从JM中从JM中分离出来的，该JM暴露了与JME一致的临床体征。通过MRI和血液采样对大脑的改变和抗病毒反应的诱导，对先前感染JMRV感染的四只动物进行了实验接种和监测。两只动物在大脑中发展出感染，其中一只动物发生双侧瘫痪。该动物被安乐死，发现表现出与MS一致的轴突病理学。 此外，我们从该菌落中的动物中分离出JMRV，该菌落被发现在脱髓鞘的JME病变中而不是在未受影响的情况下发现 大脑区域。