Li Jian-Ri, Wu Chih-Cheng, Chang Cheng-Yi, Ou Yen-Chuan, Lin Shih-Yi, Wang Ya-Yu, Chen Wen-Ying, Raung Shue-Ling, Liao Su-Lan, Chen Chun-Jung
Division of Urology, Taichung Veterans General Hospital, Taichung City, Taiwan.
Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City, Taiwan.
IUBMB Life. 2017 Feb;69(2):79-87. doi: 10.1002/iub.1595. Epub 2017 Jan 23.
Japanese encephalitis is a mosquito-borne disease caused by Japanese encephalitis virus (JEV) infection. Although JEV infects and replicates in cells with multiple tissue origins, neurons are the preferential cells for JEV infection. Currently, the identities of JEV cell tropism are largely unclear. To gain better insight into the underlying identities of JEV cell tropism, this study was designed to compare the JEV cell tropism with naïve or differentiated PC12 cells. Through nerve growth factor-differentiated PC12 cells, we discovered that JEV efficiently replicated in differentiated PC12 cells rather than naïve cells. Mechanistic studies revealed that viral adsorption/attachment seemed not to be a crucial factor. Supporting data showed that antagonizing postreceptor intracellular signaling of interferons, along with the activation of suppressor of cytokine signaling-3 (SOCS3) expression and protein tyrosine phosphatase activity, were apparent in differentiated PC12 cells after JEV infection. Independent of differentiating inducing agents, the upregulation of SOCS3 expression and protein tyrosine phosphatase activity, as well as preferential JEV tropism, were common in JEV-infected differentiated PC12 cells. Using cultured primary neurons, JEV efficiently replicated in embryonic neurons rather than adult neurons, and the preference was accompanied by higher SOCS3 expression and protein tyrosine phosphatase activity. Given that both SOCS3 and protein tyrosine phosphatases have been implicated in the process of neuronal differentiation, JEV infection seems to not only create an antagonizing strategy to escape host's interferon antiviral response but also takes advantage of cellular machinery to favor its replication. Taken together, current findings imply that dynamic changes within cellular regulators of antiviral machinery could be accompanied by events of neuronal differentiation, thus concurrently playing roles in the control of JEV cell tropism and replication. © 2017 IUBMB Life, 69(2):79-87, 2017.
日本脑炎是一种由日本脑炎病毒（JEV）感染引起的蚊媒疾病。尽管JEV可在具有多种组织来源的细胞中感染和复制，但神经元是JEV感染的优先细胞。目前，JEV细胞嗜性的特性在很大程度上尚不清楚。为了更好地了解JEV细胞嗜性的潜在特性，本研究旨在比较JEV在未分化或分化的PC12细胞中的细胞嗜性。通过神经生长因子分化的PC12细胞，我们发现JEV在分化的PC12细胞中而非未分化细胞中能高效复制。机制研究表明，病毒吸附/附着似乎不是关键因素。支持数据显示，JEV感染后，在分化的PC12细胞中，对抗干扰素的受体后细胞内信号传导，以及细胞因子信号传导抑制因子3（SOCS3）表达和蛋白酪氨酸磷酸酶活性的激活是明显的。与分化诱导剂无关，SOCS3表达和蛋白酪氨酸磷酸酶活性的上调以及JEV的优先嗜性在JEV感染的分化PC12细胞中很常见。使用培养的原代神经元，JEV在胚胎神经元中而非成年神经元中能高效复制，并且这种偏好伴随着更高的SOCS3表达和蛋白酪氨酸磷酸酶活性。鉴于SOCS3和蛋白酪氨酸磷酸酶都与神经元分化过程有关，JEV感染似乎不仅创造了一种对抗策略来逃避宿主的干扰素抗病毒反应，而且还利用细胞机制来促进其复制。综上所述，目前的研究结果表明，抗病毒机制的细胞调节因子内的动态变化可能伴随着神经元分化事件，从而在控制JEV细胞嗜性和复制中同时发挥作用。©2017国际生物化学与分子生物学联盟生命科学，69(2):79 - 87，2017。
