Bian Peiyu, Zheng Xuyang, Wei Li, Ye Chuantao, Fan Hong, Cai Yanhui, Zhang Ying, Zhang Fanglin, Jia Zhansheng, Lei Yingfeng
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University Xi'an, China.
Front Microbiol. 2017 Feb 28;8:303. doi: 10.3389/fmicb.2017.00303. eCollection 2017.
Japanese encephalitis virus (JEV) is the most prevalent cause of viral encephalitis in Asia and the western Pacific. Neuronal death caused by JEV infection and inflammation induced cytotoxicity leads to progression and deterioration of Japanese encephalitis (JE). Mixed-lineage kinase domain-like protein (MLKL) mediated necroptosis is a newly discovered pathway of programmed cell death and participates in many inflammatory diseases. In this study, we demonstrated for the first time that necroptosis was involved in the neuronal loss during JE via immune-electron microscopy and immunochemistry. The expression of MLKL in neurons was upregulated in presence of JEV infection and . Deletion of MLKL alleviated the progression of JE and decreased the level of inflammatory cytokines in mice model. Taken together, this study provides evidence for the participation of necroptosis in the pathogenesis of JEV infection.
日本脑炎病毒（JEV）是亚洲和西太平洋地区病毒性脑炎最常见的病因。JEV感染导致的神经元死亡以及炎症诱导的细胞毒性会导致日本脑炎（JE）的进展和恶化。混合谱系激酶结构域样蛋白（MLKL）介导的坏死性凋亡是新发现的程序性细胞死亡途径，并参与多种炎症性疾病。在本研究中，我们首次通过免疫电子显微镜和免疫化学证明坏死性凋亡参与了JE期间的神经元损失。在JEV感染的情况下，神经元中MLKL的表达上调。在小鼠模型中，敲除MLKL可缓解JE的进展并降低炎性细胞因子水平。综上所述，本研究为坏死性凋亡参与JEV感染的发病机制提供了证据。
