Cargando…

Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)

Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is an important pathogen that causes human and animal infectious diseases in Asia. So far, no effective antiviral agents are available to treat JEV infection. Here, we found that LDLR is a host factor required for JEV entry. Berbam...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Lihong, Li, Huanan, Ye, Zuodong, Xu, Qiang, Fu, Qiang, Sun, Wei, Qi, Wenbao, Yue, Jianbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238074/
https://www.ncbi.nlm.nih.gov/pubmed/34102949
http://dx.doi.org/10.1080/22221751.2021.1941276
_version_ 1783714835875233792
author Huang, Lihong
Li, Huanan
Ye, Zuodong
Xu, Qiang
Fu, Qiang
Sun, Wei
Qi, Wenbao
Yue, Jianbo
author_facet Huang, Lihong
Li, Huanan
Ye, Zuodong
Xu, Qiang
Fu, Qiang
Sun, Wei
Qi, Wenbao
Yue, Jianbo
author_sort Huang, Lihong
collection PubMed
description Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is an important pathogen that causes human and animal infectious diseases in Asia. So far, no effective antiviral agents are available to treat JEV infection. Here, we found that LDLR is a host factor required for JEV entry. Berbamine significantly decreases the level of LDLR at the plasma membrane by inducing the secretion of LDLR via extracellular vesicles (EVs), thereby inhibiting JEV infection. Mechanistically, berbamine blocks TRPMLs (Ca(2+) permeable non-selective cation channels in endosomes and lysosomes) to compromise the endolysosomal trafficking of LDLR. This leads to the increased secretion of LDLR via EVs and the concomitant decrease in its level at the plasma membrane, thereby rendering cells resistant to JEV infection. Berbamine also protects mice from the lethal challenge of JEV. In summary, these results indicate that berbamine is an effective anti-JEV agent by preventing JEV entry.
format Online
Article
Text
id pubmed-8238074
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-82380742021-07-07 Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR) Huang, Lihong Li, Huanan Ye, Zuodong Xu, Qiang Fu, Qiang Sun, Wei Qi, Wenbao Yue, Jianbo Emerg Microbes Infect Research Article Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is an important pathogen that causes human and animal infectious diseases in Asia. So far, no effective antiviral agents are available to treat JEV infection. Here, we found that LDLR is a host factor required for JEV entry. Berbamine significantly decreases the level of LDLR at the plasma membrane by inducing the secretion of LDLR via extracellular vesicles (EVs), thereby inhibiting JEV infection. Mechanistically, berbamine blocks TRPMLs (Ca(2+) permeable non-selective cation channels in endosomes and lysosomes) to compromise the endolysosomal trafficking of LDLR. This leads to the increased secretion of LDLR via EVs and the concomitant decrease in its level at the plasma membrane, thereby rendering cells resistant to JEV infection. Berbamine also protects mice from the lethal challenge of JEV. In summary, these results indicate that berbamine is an effective anti-JEV agent by preventing JEV entry. Taylor & Francis 2021-06-26 /pmc/articles/PMC8238074/ /pubmed/34102949 http://dx.doi.org/10.1080/22221751.2021.1941276 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Lihong
Li, Huanan
Ye, Zuodong
Xu, Qiang
Fu, Qiang
Sun, Wei
Qi, Wenbao
Yue, Jianbo
Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title_full Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title_fullStr Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title_full_unstemmed Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title_short Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)
title_sort berbamine inhibits japanese encephalitis virus (jev) infection by compromising tprmls-mediated endolysosomal trafficking of low-density lipoprotein receptor (ldlr)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238074/
https://www.ncbi.nlm.nih.gov/pubmed/34102949
http://dx.doi.org/10.1080/22221751.2021.1941276
work_keys_str_mv AT huanglihong berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT lihuanan berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT yezuodong berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT xuqiang berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT fuqiang berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT sunwei berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT qiwenbao berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr
AT yuejianbo berbamineinhibitsjapaneseencephalitisvirusjevinfectionbycompromisingtprmlsmediatedendolysosomaltraffickingoflowdensitylipoproteinreceptorldlr