HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling.
HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling.
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DOI：
10.1097/wnr.0b013e3283329c05
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发表时间：
2009-10-28
期刊：
影响因子：
1.7
通讯作者：
Lukiw WJ
中科院分区：
文献类型：
--
作者：
Hill JM;Zhao Y;Clement C;Neumann DM;Lukiw WJ
人类脑细胞的单纯疱疹病毒1型（HSV-1）感染诱导基因表达的变化，所述变化有利于感染剂的繁殖并且不利于宿主细胞的功能。我们报告了用高表型再活化剂HSV-1（17 syn+）感染人类原代神经细胞诱导脑富集的microRNA（miRNA）-146a上调，该miRNA-146a与应激脑细胞和阿尔茨海默病中的促炎信号传导相关。细胞质磷脂酶A2、诱导型前列腺素合酶环氧合酶-2和神经炎性细胞因子白细胞介素-1 β的表达均上调。脑中已知的miRNA-146 a靶点补体因子H被下调。这些数据表明HSV-1诱导的miRNA-146 a在HSV-1从补体系统逃逸中的作用，以及已知有助于阿尔茨海默型神经病理学变化的花生四烯酸级联的关键元件的激活。
Herpes simplex virus type-1 (HSV-1) infection of human brain cells induces changes in gene expression favorable to the propagation of the infecting agent and detrimental to the function of the host cells. We report that infection of human primary neural cells with a high phenotypic reactivator HSV-1 (17syn +) induces upregulation of a brain-enriched microRNA (miRNA)-146a that is associated with proinflammatory signaling in stressed brain cells and Alzheimer’s disease. Expression of cytoplasmic phospholipase A2, the inducible prostaglandin synthase cyclooxygenase-2, and the neuroinflammatory cytokine interleukin-1β were each upregulated. A known miRNA-146a target in the brain, complement factor H, was downregulated. These data suggest a role for HSV-1-induced miRNA-146a in the evasion of HSV-1 from the complement system, and the activation of key elements of the arachidonic acid cascade known to contribute to Alzheimer-type neuropathological change.