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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它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，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候选病毒，因为多发性硬化症患者的感染率较高。为了开发多发性硬化症的非人类灵长类动物模型，我们鉴定了一种在多发性硬化症患者中自发发生的新型脑脊髓炎。俄勒冈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患有这种疾病，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。伴随着广泛的星形胶质细胞增生，该群体中大约 10% 的动物出现慢性、通过磁共振成像 (MRI) 评估的亚临床病变表明，特定谱系的动物比其他谱系更容易患这种疾病，这表明 JME 具有遗传倾向。在这些研究中，我们研究了一种新型 γ- 的作用。疱疹病毒，简称日本猕猴鼻病毒（JMRV），从JM的脊髓中分离出来，表现出与JME一致的临床症状。实验性地接种了先前感染过 JMRV 的小鼠，并通过 MRI 和血液采样监测了两只动物的大脑变化和抗病毒反应的诱导，其中一只动物出现了双侧瘫痪。表现出与 MS 一致的轴突病理学。 此外，我们从该群体的动物中分离出了 JMRV，该病毒存在于脱髓鞘 JME 病变中，而不是未受影响的 JME 病变中。 大脑区域。