title: MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice.
abstract: 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 infectionin vitroandin vivo. 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.
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Bian
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Chuantao
authors.initials: C
authors.lastname: Ye
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Zhansheng
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University Xi'an, China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Lei
keywords: Japanese encephalitis virus; MLKL; inflammation; necroptosis; neuronal death