title: The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus.
abstract: The host-virus interaction during the cellular entry of Japanese encephalitis virus (JEV) is poorly characterized. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. Here, we showed that the proteasome inhibitors, MG132 and lactacystin, impaired the productive entry of JEV by effectively interfering with viral intracellular trafficking at the stage between crossing cell membrane and the initial translation of the viral genome after uncoating. Using confocal microscopy, it was demonstrated that a proportion of the internalized virions were misdirected to lysosomes following treatment with MG132, resulting in non-productive entry. In addition, using specific siRNAs targeting ubiquitin, we verified that protein ubiquitination was involved in the entry of JEV. Overall, our study demonstrated the UPS is essential for the productive entry of JEV and might represent a potential antiviral target for JEV infection.
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors: Shaobo
authors: S
authors: Wang
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors: Haibin
authors: H
authors: Liu
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China; College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China.
authors: Xiangyang
authors: X
authors: Zu
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors: Yang
authors: Y
authors: Liu
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors: Liman
authors: L
authors: Chen
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors: Xueqin
authors: X
authors: Zhu
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors: Leike
authors: L
authors: Zhang
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors: Zheng
authors: Z
authors: Zhou
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address: xiaogf@wh.iov.cn.
authors: Gengfu
authors: G
authors: Xiao
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address: wangwei@wh.iov.cn.
authors: Wei
authors: W
authors: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D004664:Encephalitis Virus, Japanese / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D057646:Virus Uncoating / Q000187:drug effects
chemical_list: D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Cellular trafficking; Japanese encephalitis virus; Lysosome; Productive entry; Ubiquitin-proteasome system; Ubiquitination