Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus

Abstract Japanese encephalitis virus (JEV) is a neurotropic zoonotic pathogen that poses a serious threat to public health. Currently, there is no specific therapeutic agent available for JEV infection, primarily due to the complexity of its infection mechanism and pathogenesis. Extracellular vesicl...

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Main Authors: Junyao Xiong, Ling'en Yang, Xiaowei Nan, Shuo Zhu, Mengxue Yan, Shengxian Xiang, Luping Zhang, Qi Li, Chengjie Yang, Xugang Wang, Ning Wei, Huanchun Chen, Youhui Si, Shengbo Cao, Jing Ye
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Extracellular Vesicles
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Online Access:https://doi.org/10.1002/jev2.70033
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author Junyao Xiong
Ling'en Yang
Xiaowei Nan
Shuo Zhu
Mengxue Yan
Shengxian Xiang
Luping Zhang
Qi Li
Chengjie Yang
Xugang Wang
Ning Wei
Huanchun Chen
Youhui Si
Shengbo Cao
Jing Ye
author_facet Junyao Xiong
Ling'en Yang
Xiaowei Nan
Shuo Zhu
Mengxue Yan
Shengxian Xiang
Luping Zhang
Qi Li
Chengjie Yang
Xugang Wang
Ning Wei
Huanchun Chen
Youhui Si
Shengbo Cao
Jing Ye
author_sort Junyao Xiong
collection DOAJ
description Abstract Japanese encephalitis virus (JEV) is a neurotropic zoonotic pathogen that poses a serious threat to public health. Currently, there is no specific therapeutic agent available for JEV infection, primarily due to the complexity of its infection mechanism and pathogenesis. Extracellular vesicles (EVs) have been known to play an important role in viral infection, but their specific functions in JEV infection remain unknown. Here, ultracentrifugation in combination with density gradient centrifugation was conducted to purify EVs from JEV‐infected cells. The purified EVs were found to be infectious, with virions observed inside the EVs. Furthermore, our study showed the formation process of virion‐containing EVs both in vitro and in vivo, which involved the fusion of multivesicular bodies with the cell membrane, leading to the release of virion‐containing intraluminal vesicles into the extracellular space. Further studies revealed that EVs played a crucial role in JEV propagation by facilitating viral entry and assembly‐release. Furthermore, EVs assisted JEV in evading the neutralizing antibodies and promoted viral capability to cross the blood‐brain and placental barriers. Moreover, in vivo experiments demonstrated that EVs were beneficial for JEV infection and pathogenicity. Taken together, our findings highlight the significant contribution of EVs in JEV infection and provide valuable insights into JEV pathogenesis.
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record_format Article
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spelling doaj-art-a4fbdd1618074a519f8302452be9caa52025-08-20T02:41:52ZengWileyJournal of Extracellular Vesicles2001-30782025-01-01141n/an/a10.1002/jev2.70033Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virusJunyao Xiong0Ling'en Yang1Xiaowei Nan2Shuo Zhu3Mengxue Yan4Shengxian Xiang5Luping Zhang6Qi Li7Chengjie Yang8Xugang Wang9Ning Wei10Huanchun Chen11Youhui Si12Shengbo Cao13Jing Ye14National Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaNational Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan Hubei ChinaAbstract Japanese encephalitis virus (JEV) is a neurotropic zoonotic pathogen that poses a serious threat to public health. Currently, there is no specific therapeutic agent available for JEV infection, primarily due to the complexity of its infection mechanism and pathogenesis. Extracellular vesicles (EVs) have been known to play an important role in viral infection, but their specific functions in JEV infection remain unknown. Here, ultracentrifugation in combination with density gradient centrifugation was conducted to purify EVs from JEV‐infected cells. The purified EVs were found to be infectious, with virions observed inside the EVs. Furthermore, our study showed the formation process of virion‐containing EVs both in vitro and in vivo, which involved the fusion of multivesicular bodies with the cell membrane, leading to the release of virion‐containing intraluminal vesicles into the extracellular space. Further studies revealed that EVs played a crucial role in JEV propagation by facilitating viral entry and assembly‐release. Furthermore, EVs assisted JEV in evading the neutralizing antibodies and promoted viral capability to cross the blood‐brain and placental barriers. Moreover, in vivo experiments demonstrated that EVs were beneficial for JEV infection and pathogenicity. Taken together, our findings highlight the significant contribution of EVs in JEV infection and provide valuable insights into JEV pathogenesis.https://doi.org/10.1002/jev2.70033EVsJEVneutralizing antibodiespathogenicitytissue barrier
spellingShingle Junyao Xiong
Ling'en Yang
Xiaowei Nan
Shuo Zhu
Mengxue Yan
Shengxian Xiang
Luping Zhang
Qi Li
Chengjie Yang
Xugang Wang
Ning Wei
Huanchun Chen
Youhui Si
Shengbo Cao
Jing Ye
Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
Journal of Extracellular Vesicles
EVs
JEV
neutralizing antibodies
pathogenicity
tissue barrier
title Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
title_full Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
title_fullStr Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
title_full_unstemmed Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
title_short Extracellular vesicles promote the infection and pathogenicity of Japanese encephalitis virus
title_sort extracellular vesicles promote the infection and pathogenicity of japanese encephalitis virus
topic EVs
JEV
neutralizing antibodies
pathogenicity
tissue barrier
url https://doi.org/10.1002/jev2.70033
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