2. Academic Validation
  3. The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus

The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus

  • Virology. 2016 Nov;498:116-127. doi: 10.1016/j.virol.2016.08.013.
Shaobo Wang 1,  Haibin Liu 2,  Xiangyang Zu 3,  Yang Liu 2,  Liman Chen 1,  Xueqin Zhu 1,  Leike Zhang 1,  Zheng Zhou 1,  Gengfu Xiao 4,  Wei Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
  • 2 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 3 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.
  • 4 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.
  • 5 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.
PMID: 27567260 DOI: 10.1016/j.virol.2016.08.013
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.

Keywords

Cellular trafficking; Japanese encephalitis virus; Lysosome; Productive entry; Ubiquitin-proteasome system; Ubiquitination.

Figures
Products