Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses

Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses
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DOI:
10.1016/j.virol.2010.01.025
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发表时间:
2010-05-10
期刊:
影响因子:
3.7
通讯作者:
Grdzelishvili, Valery Z.
Grdzelishvili, Valery Z.
中科院分区:
医学3区
文献类型:
--
作者:
Chauhan, Vinita S.;Furr, Samantha R.;Grdzelishvili, Valery Z.

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通过鼻内给药感染水疱性口炎病毒(VSV)可导致小胶质细胞和星形胶质细胞迅速激活和增殖的严重脑炎。我们最近发现这些胶质细胞表达rig - 1和MDA5,它们是病毒RNA的细胞质模式识别受体。然而,目前尚不清楚VSV是否可以在神经胶质细胞中复制,或者这种复制是否需要它们的炎症反应。在这里,我们证明了初级小胶质细胞和星形胶质细胞允许VSV感染和有限的生产性复制。重要的是,我们发现病毒复制是这些细胞产生强大炎症介质所必需的。最后,我们已经证实,在体内VSV给药可导致胶质细胞原位病毒感染。这些结果表明,病毒在神经胶质细胞内的复制可能在VSV和其他嗜神经性非节段负链RNA病毒感染后的中枢神经系统炎症中起重要作用。(C) 2010爱思唯尔公司版权所有。
Vesicular stomatitis virus (VSV) infection of mice via intranasal administration results in a severe encephalitis with rapid activation and proliferation of microglia and astrocytes. We have recently shown that these glial cells express RIG-I and MDA5, cytosolic pattern recognition receptors for viral RNA. However, it is unclear whether VSV can replicate in glial cells or if such replication is required for their inflammatory responses. Here we demonstrate that primary microglia and astrocytes are permissive for VSV infection and limited productive replication. Importantly, we show that viral replication is required for robust inflammatory mediator production by these cells. Finally, we have confirmed that in vivo VSV administration can result in viral infection of glial cells in situ. These results suggest that viral replication within resident glial cells might play an important role in CNS inflammation following infection with VSV and possibly other neurotropic nonsegmented negative-strand RNA viruses. (C) 2010 Elsevier Inc. All rights reserved.