GAMMA-2 HERPESVIRUS-ASSOCIATED JAPANESE MACAQUE ENCEPHALOMYELITIS

这个子项目是众多研究子项目之一

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.