Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits myelination.
Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits myelination.
复制标题
通过非裂解性沙粒病毒感染靶向雪旺细胞选择性抑制髓鞘形成。
DOI：
10.1073/pnas.2232366100
复制
发表时间：
2003
影响因子：
11.1
通讯作者：
Oldstone,MichaelBA
中科院分区：
文献类型：
--
作者：
Rambukkana,Anura;Kunz,Stefan;Min,Jenny;Campbell,KevinP;Oldstone,MichaelBA
沙粒病毒家族的成员以其出血综合征而闻名，引起不同的神经系统疾病;然而，与这些病毒相关的外周神经系统疾病的细胞和分子靶点以及发病机制尚不清楚。使用非细胞溶解性淋巴细胞性脉络丛脑膜炎病毒、沙粒病毒原型和假型拉沙热病毒，我们发现雪旺细胞而不是神经元优先被靶向和窝藏病毒。这种宽容性是由病毒糖蛋白使用其受体α-肌营养不良聚糖引起的，α-肌营养不良聚糖在雪旺细胞膜上高度丰富。持续性淋巴细胞性脉络丛脑膜炎病毒感染使未成熟的雪旺细胞有缺陷或不能形成致密的髓鞘时，他们分化成髓鞘表型的雪旺细胞的anin vitrodifferentiation模型。持续感染不引起雪旺细胞凋亡或细胞病变。髓鞘形成的缺陷与肌营养不良蛋白聚糖表达的下调和层粘连蛋白-2组织的破坏以及雪旺细胞轴突单位上的基底层组装一致。这些数据提供了证据，层粘连蛋白-2-层粘连蛋白-2受体通讯途径在周围神经系统的非溶解性病毒和由此产生的髓鞘缺陷，这可能部分有助于与沙粒病毒感染相关的神经异常的选择性扰动。
Members of the arenavirus family, famous for their hemorrhagic syndromes, cause distinct neurological disorders; however, cellular and molecular targets as well as pathogenesis of peripheral nervous system disorders associated with these viruses are unknown. Using noncytolytic lymphocytic choriomeningitis virus, the prototype arenavirus, and pseudotyped Lassa fever virus, we showed that the Schwann cells, but not the neurons, were preferentially targeted and harbored the virus. This permissiveness was caused by the viral glycoprotein usage of its receptor α-dystroglycan, which was highly abundant on Schwann cell membranes. Persistent lymphocytic choriomeningitis virus infection rendered immature Schwann cells defective or incapable of forming compact myelin sheathes when they differentiated to myelinating phenotype in anin vitrodifferentiation model of Schwann cells. Persistent infection did not cause Schwann cell apoptosis or cytopathic effect. Defects in myelination coincided with the down-regulation of dystroglycan expression and disruption of the laminin-2 organization and basal lamina assembly on Schwann cell-axon units. The data provide evidence for a selective perturbation of laminin-2-laminin-2 receptor communication pathway in the peripheral nervous system by a nonlytic virus and the resulting myelin defects, which may partly contribute to neurological abnormalities associated with arenaviral infection.