Kaliyaperumal Saravanan, Wüthrich Christian, Westmoreland Susan V, Koralnik Igor J
From the New England Primate Research Center, Harvard Medical School, Southborough (SK, SVW); and Division of Neuro-Immunology, Department of Neurology, Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston (CW, IJK), Massachusetts.
J Neuropathol Exp Neurol. 2015 Nov;74(11):1071-6. doi: 10.1097/NEN.0000000000000252.
Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the CNS that usually develops in immunocompromised individuals because of reactivation of quiescent JC virus (JCV). There are only a few reports of JCV infection in the human spinal cord. Progressive multifocal leukoencephalopathy-like demyelinating lesions have been documented in the brains of simian immunodeficiency virus-infected macaques. To determine whether simian virus 40 (SV40) can infect and cause PML lesions in spinal cords of immunosuppressed macaques, we examined archival spinal cord samples from 15 simian immunodeficiency virus-infected rhesus monkeys with acquired immunodeficiency syndrome and SV40 infection of the brain. Among those, 6 (40%) had SV40-infected cells in the spinal cord, including 1 with PML-like lesions, 1 with PML-like lesions and meningoencephalitis, 2 with meningoencephalitis, 1 with gray matter gliosis, and 1 with no lesions. One animal with a large PML-like lesion had extensive demyelination and SV40 infection of astrocytes, oligodendrocytes, and meningeal cells. None of the 6 animals had SV40-infected spinal cord neurons. These observations indicate that, like JCV in immunosuppressed humans, SV40 can infect glial cells and cause PML-like lesions in the spinal cord of immunosuppressed rhesus macaques. Rhesus macaques could serve as an animal model to study polyomavirus infection and pathogenesis in the spinal cord.
进行性多灶性白质脑病(PML)是一种中枢神经系统的常致命性脱髓鞘疾病,通常在免疫功能低下的个体中因潜伏的JC病毒(JCV)重新激活而发病。关于JCV感染人类脊髓的报道仅有少数几例。在感染猿猴免疫缺陷病毒的猕猴大脑中已记录到类似进行性多灶性白质脑病的脱髓鞘病变。为了确定猿猴病毒40(SV40)是否能感染免疫抑制猕猴的脊髓并导致PML病变,我们检查了15只感染猿猴免疫缺陷病毒且患有获得性免疫缺陷综合征并伴有SV40脑部感染的恒河猴的存档脊髓样本。其中,6只(40%)脊髓中有SV40感染的细胞,包括1只患有类似PML病变的、1只患有类似PML病变并伴有脑膜脑炎的、2只患有脑膜脑炎的、1只患有灰质胶质增生的以及1只无病变的。1只患有大类似PML病变的动物出现广泛脱髓鞘,且星形胶质细胞、少突胶质细胞和脑膜细胞均有SV40感染。6只动物中没有一只脊髓神经元有SV40感染。这些观察结果表明,与免疫抑制人类中的JCV一样,SV40可感染神经胶质细胞并在免疫抑制的恒河猴脊髓中导致类似PML的病变。恒河猴可作为研究脊髓中多瘤病毒感染和发病机制的动物模型。