Effects of Toll-like receptor 3 on herpes simplex virus type-1-infected mouse neural stem cells.
Effects of Toll-like receptor 3 on herpes simplex virus type-1-infected mouse neural stem cells.
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DOI：
10.1139/cjm-2014-0540
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发表时间：
2015-03
影响因子：
2.8
通讯作者：
Xiuning Sun;Lihong Shi;Haoyun Zhang;Ruifang Li;Ruiwen Liang;Zhijun Liu
中科院分区：
文献类型：
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作者：
Xiuning Sun;Lihong Shi;Haoyun Zhang;Ruifang Li;Ruiwen Liang;Zhijun Liu
本研究旨在探讨1型单纯疱疹病毒（HSV-1）感染对干扰素调节因子3 （IRF3）磷酸化和干扰素β (IFN-β)表达的影响，并阐明toll样受体3 （TLR3）在感染HSV-1的小鼠神经干细胞（NSCs）中的功能。在hsv -1感染的培养NSCs中，采用免疫荧光、逆转录聚合酶链反应、Western blot和ELISA检测TLR3、IRF3和IFN-β的表达模式。然后利用慢病毒介导的RNA干扰（RNAi）阻断TLR3的表达，研究其对宿主抵抗HSV-1感染的影响。在未感染条件下，NSCs表达TLR3和磷酸化IRF3，但感染后，TLR3表达水平上调，细胞核内IRF3磷酸化水平显著增强，同时IFN-β也有表达。慢病毒介导的RNAi阻断TLR3表达后，IRF3磷酸化和IFN-β表达下调。因此，在IRF3被磷酸化诱导IFN-β表达后，HSV-1上调了NSCs中TLR3的表达，促进了核易位。TLR3通过先天免疫功能表现出抗hsv -1感染的能力。
In this study, we aimed to investigate the effect of herpes simplex virus type-1 (HSV-1) infection on the phosphorylation of interferon regulatory factor 3 (IRF3) and the expression of interferon-β (IFN-β), as well as to clarify the functions of toll-like receptor 3 (TLR3) in mouse neural stem cells (NSCs) infected with HSV-1. In HSV-1-infected cultured NSCs, immunofluorescence, reverse transcription - polymerase chain reaction, Western blot, and ELISA were performed to reveal the expression patterns of TLR3, IRF3, and IFN-β. Then, lentivirus-mediated RNA interference (RNAi) was used to block the expression of TLR3, and its effect on host resistance to HSV-1 infection was investigated. Under uninfected conditions, NSCs expressed TLR3 and phosphorylated IRF3, but after infection, the expression level of TLR3 was upregulated and the phosphorylation level of IRF3 in the nucleus was significantly enhanced, while IFN-β was also expressed. After TLR3 expression was blocked by lentivirus-mediated RNAi, IRF3 phosphorylation and IFN-β expression were downregulated. Therefore, HSV-1 upregulated the expression of TLR3 in NSCs and promoted nuclear translocation after IRF3 was phosphorylated to induce IFN-β expression. TLR3 exhibited an anti-HSV-1 infection capacity via innate immune functions.