Nature：揭示西尼罗河病毒导致记忆丧失机制
在一项新的研究中，来自美国华盛顿大学和科罗拉多大学等机构的研究人员发现最为严重的西尼罗河病毒（West Nile virus, WNV）感染如何导致记忆丧失和情感障碍，从而为开发出治疗这种蚊子传播疾病的新疗法开辟新的道路。相关研究结果于2016年6月22日在线发表在Nature期刊上，论文标题为“A complement–microglial axis drives synapse loss during virus-induced memory impairment”。在最为严重的西尼罗河病毒感染中存活下来的病人当中，有50%的人经常产生记忆丧失、学习障碍、无法集中精力和易怒等症状。在此之前，这一现象发生的具体原因一直是个迷。
在这项研究中，研究人员发现这种病毒并不杀死神经元，但是触发它们产生减少突触的炎症，其中突触是神经细胞之间传递信息的连接结构。
论文共同作者、科罗拉多大学医学院神经内科主任Kenneth Tyler博士说，“在先在小鼠中发现随后在人类中证实并不是神经元死亡导致记忆丧失，而是神经细胞之间的突触减少。这种病毒感染激活小胶质细胞和补体途径，它们有助抵抗这种感染但最终会破坏突触。”
研究人员发现感染上西尼罗河病毒的小鼠很难从迷宫中走出来，但是健康的小鼠很快地找到出口。他们随后发现被西尼罗河病毒感染的小鼠遭受严重突触损伤。此外，他们研究了死于西尼罗河病毒感染的患者的大脑组织，也发现了同样的现象。
Tyler说，在美国，西尼罗河病毒是急性病毒性脑炎的主要病因，尽管这是相对罕见的。他说，在每100名感染上西尼罗河病毒的患者当中，大约就有一人遭受最为严重的感染。
在二十世纪九十年代后期，西尼罗河病毒在美国出现，从那之后一直是一种持续性威胁。去年，加利福尼亚州有730例病例，德克萨斯州有252例病例，科罗拉多州有201例病例。在科罗拉多州，这些病例包括57例神经感染性的病例（最为严重的病例）和2例死亡。
Tyler说，“这一发现为在小鼠体内测试疗法和药物提供机会。我们已有一些药物可能是治疗这种疾病的好的候选物。”
避免西尼罗河病毒感染的最好方法就是穿长袖衣服、使用驱蚊剂和远离有积水的地方。携带这种病毒的蚊子在黄昏和破晓时最为活跃。
原文题目：A complement–microglial axis drives synapse loss during virus-induced memory impairmentAbstract
Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae1, 2. Although thousands of cases of WNV-mediated memory dysfunction accrue annually3, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development4, 5. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein6, 7 leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34−/− mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.来源：生物谷
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