GAMMA-2 HERPESVIRUS-ASSOCIATED JAPANESE MACAQUE ENCEPHALOMYELITIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多发性硬化症(MS)是一种多因素引起的自身免疫性疾病，推测与病毒感染、宿主遗传易感性和环境因素有关。在已知的感染人类的病毒中，伽玛疱疹病毒被认为是领先的候选病毒，因为多发性硬化症患者对这些病毒的抗体效价较高，而从多发性硬化症患者脑组织中提取的样本具有病毒特异性T细胞。为了开发多发性硬化症的非人类灵长类动物模型，我们在俄勒冈州国家灵长类研究中心描述了一种新的脑脊髓炎，这种脑脊髓炎在俄勒冈州国家灵长类动物研究中心的一小部分日本猕猴(JM)中自发发生。这种疾病被称为日本猕猴脑脊髓炎(JME)，既有进展性的，也有复发缓解性的，其特征是大脑和脊髓脱髓鞘，并伴有广泛的星形胶质细胞增生。受影响的动物会出现令人衰弱的运动和眼睛障碍。根据磁共振成像(MRI)的评估，这个群体中大约10%的动物似乎有慢性亚临床损害。系谱分析表明，特定的动物谱系比其他动物更容易感染这种疾病，这表明JME具有遗传易感性。在这些研究中，我们研究了一种新的伽玛疱疹病毒的作用，被称为日本猕猴横纹夜蛾病毒(JMRV)，从表现出与JME一致的临床症状的JM的脊髓中分离出来。对4只新感染JMRV的动物进行了实验接种，并通过MRI和采血监测脑组织的变化和抗病毒反应的诱导。两只动物出现了脑部炎症，其中一只出现了双侧瘫痪。这只动物被实施了安乐死，并发现其轴突病理与MS一致。 此外，我们已经从这个群体中的动物身上分离出JMRV，这种病毒是在脱髓鞘的JME病变中发现的，而不是在未受影响的病变中发现的。 大脑的不同区域。

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.