PNAS：流感和慢性疾病之间的联系

科学家发现了一种高致病性H5N1禽流感病毒毒株可以进入大脑并对数十年后帕金森病等神经退行性疾病的发展有贡献。这项研究为一种假说提供了证据，即病毒可以增加出现某些严重的慢性疾病的风险，而这些疾病看上去似乎与最初的病毒感染无关。

Richard Smeyne及其同事发现了一种H5N1毒株进入了小鼠大脑并且导致了帕金森病的几种基本特征，包括颤抖、运动障碍以及失去脑细胞。这种细胞损失本身不足以导致帕金森病，因为小鼠的免疫系统可以从大脑中清除这种病毒，但是小鼠的免疫系统被置于一个长期激活的状态。这种激活后来导致了诸如帕金森病和阿兹海默病等疾病典型的蛋白质集合。神经疾病群发有时候跟随着流感大流行暴发而出现，但是很难在两者之间找到分子的联系。

这组作者说，这项研究为“击跑”的理论提供了支持，该理论认为迅速从身体中清除一种病毒感染可能让免疫系统激活，而让大脑对于未来的另一种可能与其无关的来源造成的破坏变得脆弱。（生物谷Bioon.com）

生物谷推荐原始出处：

PNAS August 10, 2009, doi: 10.1073/pnas.0900096106

Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration

Haeman Janga,b, David Boltzc, Katharine Sturm-Ramirezc,1, Kennie R. Shepherda,2, Yun Jiaoa, Robert Websterc and Richard J. Smeynea,3

Departments of aDevelopmental Neurobiology and
cInfectious Diseases/Virology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678; and
bIntegrated Program in Biomedical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163

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.