Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration
Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration
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DOI：
10.1073/pnas.0900096106
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发表时间：
2009-08-18
影响因子：
11.1
通讯作者：
Smeyne, Richard J.
中科院分区：
文献类型：
--
作者：
Jang, Haeman;Boltz, David;Smeyne, Richard J.
目前最大的流感大流行威胁之一是高致病性H5 N1禽流感病毒。迄今为止，在已知的433例人类H5 N1感染病例中，有61%被证明是致命的。感染H5 N1病毒的动物表现出急性神经系统症状，从轻度脑炎到运动障碍到昏迷。然而，没有研究检查H5 N1感染存活宿主的长期神经系统后果。使用C57 BL/6 J小鼠，一种可以被A/Vietnam/1203/04 H5 N1病毒感染而不适应的小鼠品系，我们表明这种病毒从外周神经系统进入CNS到更高水平的神经轴。在H5 N1病毒感染的区域，我们观察到小胶质细胞和α-突触核蛋白磷酸化和聚集的激活，在感染消退后持续很长时间。我们还观察到一个显着的损失，多巴胺能神经元在黑质pars延髓感染后60天。我们的研究结果表明，大流行性H5 N1病原体，或其他嗜神经性流感病毒，可以启动中枢神经系统的蛋白质聚集疾病，包括帕金森氏症和阿尔茨海默氏症。
One of the greatest influenza pandemic threats at this time is posed by the highly pathogenic H5N1 avian influenza viruses. To date, 61% of the 433 known human cases of H5N1 infection have proved fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances to coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection among surviving hosts. Using the C57BL/6J mouse, a mouse strain that can be infected by the A/Vietnam/1203/04 H5N1 virus without adaptation, we show that this virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection. We also observe a significant loss of dopaminergic neurons in the substantia nigra pars compacta 60 days after infection. Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases.