Japanese macaque encephalomyelitis: A spontaneous multiple sclerosis–like disease in a nonhuman primate

Abstract

Objective To describe Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease occurring in the Oregon National Primate Research Center’s (ONPRC) colony of Japanese macaques (JM, Macaca fuscata). Methods JM with neurologic impairment were removed from the colony, evaluated and treated with supportive care. Animals were humanely euthanized and their central nervous system (CNS) examined. Results ONPRC’s JM colony was established in 1965 and no cases of JME occurred until 1986. Since 1986, 56 JM spontaneously developed a disease characterized clinically by paresis of one or more limbs, ataxia or ocular motor paresis. Most animals were humanely euthanized during their initial episode. Three recovered, later relapsed and were then euthanized. There was no gender predilection and the median age for disease was 4 years. Magnetic resonance imaging of eight cases of JME revealed multiple gadolinium enhancing T1-weighted hyperintensities in the white matter of the cerebral hemispheres, brainstem, cerebellum and cervical spinal cord. The CNS of monkeys with JME contained multifocal plaque-like demyelinated lesions of varying ages, including acute and chronic, active demyelinating lesions with macrophages and lymphocytic periventricular infiltrates, and chronic, inactive demyelinated lesions. A previously undescribed gamma-herpesvirus was cultured from acute JME white matter lesions. Cases of JME continue to affect 1–3% of the ONPRC colony per year. Interpretation JME is a unique spontaneous disease in a nonhuman primate that has similarities with multiple sclerosis (MS) and is associated with a novel simian herpesvirus. Elucidating the pathogenesis of JME may shed new light on MS and other human demyelinating diseases.

Genomic Characterization of Japanese Macaque Rhadinovirus, a Novel Herpesvirus Isolated from a Nonhuman Primate with a Spontaneous Inflammatory Demyelinating Disease

“…JMRV was recently isolated from a JM that developed JME, a disease that possesses clinical and histopathological features that resemble MS in humans (1). As reported here, we have fully sequenced the complete genome of JMRV, as well as two plaque isolates of this virus, the results of which provide further evidence that JMRV is a gammaherpesvirus highly similar to other human and primate gammaherpesviruses.…”

“…The identification and preliminary characterization of JMRV strain 17792 (JMRV 17792 ) was previously described (1). JMRV 17792 is referred to throughout the present study as JMRV.…”

“…e recently described the occurrence of a spontaneous demyelinating disease that possesses clinical and histopathological features resembling multiple sclerosis (MS) in a colony of Japanese macaques (JM; Macaca fuscata) housed at the Oregon National Primate Research Center (1). This disease, referred to as Japanese macaque encephalomyelitis (JME), presents with clinical features such as ataxia and paralysis and, in some cases, is associated with episodes of recovery and relapse.…”

“…Histopathological similarities with MS were also observed and were characterized by the presence of multifocal plaque-like demyelinated lesions accompanied with inflammatory cell infiltrates and loss of oligodendrocytes and axons. Of particular interest was the isolation of a novel gammaherpesvirus, referred to as Japanese macaque rhadinovirus (JMRV), from a central nervous system (CNS) lesion of a JM that had developed JME (1). JMRV was subsequently found in other JME lesions but not in normal white matter tissue of affected animals, suggesting the virus is a passenger within the inflammatory cells infiltrating the lesion or may be associated with the development of JME.…”

Complete Genome Sequence of Pig-Tailed Macaque Rhadinovirus 2 and Its Evolutionary Relationship with Rhesus Macaque Rhadinovirus and Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus

“…The RV2 rhadinovirus lineage consists of a group of more distantly related viruses, which coinfect the same Old World primate species (7,8,10,(12)(13)(14). Rhesus rhadinovirus (RRV) is the prototype macaque RV2 rhadinovirus, although closely related RV2 rhadinoviruses have also been detected in other macaque species, including MneRV2/PRV (pigtailed macaque), MfaRV2 (long-tailed macaque), and MfuRV2/ JMRV (Japanese macaque; Macaca fuscata) (8,(15)(16)(17). The macaque RV1 and RV2 rhadinoviruses are highly prevalent and persistent in captive macaque populations with infection rates exceeding 90% (16,18,19).…”