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...
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| Format: | Article |
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Taylor & Francis Group
2021-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2021.1941276 |
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| author | Lihong Huang Huanan Li Zuodong Ye Qiang Xu Qiang Fu Wei Sun Wenbao Qi Jianbo Yue |
| author_facet | Lihong Huang Huanan Li Zuodong Ye Qiang Xu Qiang Fu Wei Sun Wenbao Qi Jianbo Yue |
| author_sort | Lihong Huang |
| collection | DOAJ |
| 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 (Ca2+ 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 | Article |
| id | doaj-art-7fdf1cc4a1f54c48a1ffedc951146895 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-7fdf1cc4a1f54c48a1ffedc9511468952025-08-20T02:59:11ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011011257127110.1080/22221751.2021.1941276Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR)Lihong Huang0Huanan Li1Zuodong Ye2Qiang Xu3Qiang Fu4Wei Sun5Wenbao Qi6Jianbo Yue7City University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of ChinaJapanese 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 (Ca2+ 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.https://www.tandfonline.com/doi/10.1080/22221751.2021.1941276BerbamineflavivirusJEVLDLRCa2+TRPMLs |
| spellingShingle | Lihong Huang Huanan Li Zuodong Ye Qiang Xu Qiang Fu Wei Sun Wenbao Qi Jianbo Yue Berbamine inhibits Japanese encephalitis virus (JEV) infection by compromising TPRMLs-mediated endolysosomal trafficking of low-density lipoprotein receptor (LDLR) Emerging Microbes and Infections Berbamine flavivirus JEV LDLR Ca2+ TRPMLs |
| 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 | Berbamine flavivirus JEV LDLR Ca2+ TRPMLs |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2021.1941276 |
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