GAMMA-2 HERPESVIRUS-ASSOCIATED JAPANESE MACAQUE ENCEPHALOMYELITIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 多发性硬化症（MS）是一种多因素起源的自身免疫性疾病，推测涉及病毒感染、宿主遗传易感性和环境因素。在已知感染人类的病毒中，γ-疱疹病毒被认为是主要的候选者，因为MS患者对这些病毒具有更高的抗体滴度，并且从MS患者采集的脑样本具有病毒特异性T细胞。为了开发非人灵长类动物多发性硬化症模型，我们描述了一种新型脑脊髓炎的特征，这种脑脊髓炎在俄勒冈州国家灵长类动物研究中心的日本猕猴（JM）群体中的一小部分动物中自发发生。这种疾病被称为日本猕猴脑脊髓炎（JME），以进行性和复发缓解型两种形式发生，其特征是脑和脊髓脱髓鞘，伴有广泛的星形胶质细胞增生。受影响的动物出现衰弱性运动和眼部障碍。通过磁共振成像（MRI）评价，该群体中约10%的动物似乎存在慢性亚临床病变。系谱分析表明，特定谱系的动物比其他动物更容易感染这种疾病，这表明JME的遗传易感性。在这些研究中，我们研究了一种新的γ-疱疹病毒的作用，称为日本猕猴rhadinovirus（JMRV），从脊髓中分离的JM表现出与JME一致的临床体征。四种动物实验性接种先前感染JMRV的小鼠，并通过MRI和血液采样监测脑的改变和抗病毒应答的诱导。两只动物的脑部出现炎症，其中一只动物出现双侧瘫痪。对该动物实施安乐死，发现其轴突病理学与MS一致。 此外，我们已经从该群体中的动物中分离出了JMRV，其在脱髓鞘的JME病变中发现，而在未受影响的JME病变中没有发现。 大脑区域。

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.