Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function
Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function
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DOI：
10.1523/jneurosci.1740-17.2018
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发表时间：
2018-03-21
影响因子：
5.3
通讯作者：
Korte, Martin
中科院分区：
文献类型：
--
作者：
Hosseini, Shirin;Wilk, Esther;Korte, Martin
据报道，急性流感感染与神经系统症状有关。然而，嗜神经性和非嗜神经性甲型流感病毒（IAV）变体感染CNS的长期后果仍然难以捉摸。我们可以表明，在雌性C57 BL/6小鼠中，在用嗜神经性H7 N7（rSC 35 M）和非嗜神经性H3 N2（maHK 68）感染后，海马中的棘丢失持续远远超过疾病的急性期。尽管H7 N7或H3 N2感染后30 d脊柱数量显著减少，但完全恢复只能在120 dpi时观察到。感染H1N1病毒，这是以前显示影响脊柱数量和海马依赖性学习急性，没有显着的长期影响。脊柱丢失与激活的小胶质细胞数量增加、海马长时程增强减少以及空间记忆形成受损有关，这表明IAV相关炎症诱导了海马网络的功能和结构改变。转录组分析显示，在感染H3 N2和H7 N7的小鼠中，在感染后第18天，以及在感染H7 N7的小鼠中，在感染后第30天，许多炎性基因、神经元特异性基因和神经胶质特异性基因的调节与结构和功能改变有关。我们的数据提供的证据表明，由嗜神经性H7 N7诱导的神经炎症和用非嗜神经性H3 N2 IAV感染肺部导致CNS的长期损害。因此，人类的IAV感染不仅可能导致感染器官的短期反应，还可能引发神经炎症和CNS的相关慢性改变。
Acute influenza infection has been reported to be associated with neurological symptoms. However, the long-term consequences of an infection with neurotropic and non-neurotropic influenza A virus (IAV) variants for the CNS remain elusive. We can show that spine loss in the hippocampus after infection with neurotropic H7N7 (rSC35M) and non-neurotropic H3N2 (maHK68) in female C57BL/6 mice persists well beyond the acute phase of the disease. Although spine number was significantly reduced at 30 d postinfection (dpi) with H7N7 or H3N2, full recovery could only be observed much later at 120 dpi. Infection with H1N1 virus, which was shown previously to affect spine number and hippocampus-dependent learning acutely, had no significant long-term effects. Spine loss was associated with an increase in the number of activated microglia, reduced long-term potentiation in the hippocampus, and impairment in spatial memory formation, indicating that IAV-associated inflammation induced functional and structural alterations in hippocampal networks. Transcriptome analyses revealed regulation of many inflammatory and neuron-and glia-specific genes in H3N2- and H7N7-infected mice at day 18 and in H7N7-infected mice at day 30 pi that related to the structural and functional alterations. Our data provide evidence that neuroinflammation induced by neurotropic H7N7 and infection of the lung with a non-neurotropic H3N2 IAV result in long-term impairments in the CNS. IAV infection in humans may therefore not only lead to short-term responses in infected organs, but may also trigger neuroinflammation and associated chronic alterations in the CNS.