Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus
Abstract Hepatitis C virus (HCV) is a major human pathogen causing liver diseases. Although direct‐acting antiviral agents effectively inhibit HCV infection, cell–cell transmission remains a critical venue for HCV persistence in vivo. However, the underlying mechanism of how HCV spreads intercellula...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408917 |
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| author | Yifan Xing Zeyu Wen Jie Mei Xinyi Huang Shuangshuang Zhao Jin Zhong Yaming Jiu |
| author_facet | Yifan Xing Zeyu Wen Jie Mei Xinyi Huang Shuangshuang Zhao Jin Zhong Yaming Jiu |
| author_sort | Yifan Xing |
| collection | DOAJ |
| description | Abstract Hepatitis C virus (HCV) is a major human pathogen causing liver diseases. Although direct‐acting antiviral agents effectively inhibit HCV infection, cell–cell transmission remains a critical venue for HCV persistence in vivo. However, the underlying mechanism of how HCV spreads intercellularly remains elusive. Here, we demonstrated that vimentin, a host intermediate filaments protein, is dispensable for HCV infection in cell models but essential for simulated in vivo infection in differentiated hepatocytes. Genetic removal of vimentin markedly and specifically disrupts HCV cell–cell transmission without influencing cell‐free infection. Through mutual co‐immunoprecipitation screening, we identified that the N‐terminal 1–95 amino acids of vimentin exclusively interact with the HCV envelope protein E1. Introducing either full‐length or head region of vimentin is capable of restoring the cell–cell transmission deficiency in vimentin‐knockout cells. Moreover, we showed that it is vimentin on the plasma membrane of recipient cells that orchestrates HCV cell–cell transmission. Consequently, vimentin antibody, either applied individually or in combination with HCV neutralizing antibody, exerts pronounced inhibition of HCV cell–cell transmission. Together, the results unveil an unrecognized function of vimentin as a unique venue dominating viral transmission, providing novel insights into propelling advancements in vimentin‐targeted anti‐HCV therapies. |
| format | Article |
| id | doaj-art-af97bd71233b4bcb88a2eafef939ae02 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-af97bd71233b4bcb88a2eafef939ae022025-01-20T13:04:19ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202408917Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C VirusYifan Xing0Zeyu Wen1Jie Mei2Xinyi Huang3Shuangshuang Zhao4Jin Zhong5Yaming Jiu6University of Chinese Academy of Sciences Yuquan Road No. 19(A) Shijingshan District Beijing 100049 P. R. ChinaKey Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences Shanghai 200031 P. R. ChinaUniversity of Chinese Academy of Sciences Yuquan Road No. 19(A) Shijingshan District Beijing 100049 P. R. ChinaKey Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences Shanghai 200031 P. R. ChinaKey Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences Shanghai 200031 P. R. ChinaUniversity of Chinese Academy of Sciences Yuquan Road No. 19(A) Shijingshan District Beijing 100049 P. R. ChinaUniversity of Chinese Academy of Sciences Yuquan Road No. 19(A) Shijingshan District Beijing 100049 P. R. ChinaAbstract Hepatitis C virus (HCV) is a major human pathogen causing liver diseases. Although direct‐acting antiviral agents effectively inhibit HCV infection, cell–cell transmission remains a critical venue for HCV persistence in vivo. However, the underlying mechanism of how HCV spreads intercellularly remains elusive. Here, we demonstrated that vimentin, a host intermediate filaments protein, is dispensable for HCV infection in cell models but essential for simulated in vivo infection in differentiated hepatocytes. Genetic removal of vimentin markedly and specifically disrupts HCV cell–cell transmission without influencing cell‐free infection. Through mutual co‐immunoprecipitation screening, we identified that the N‐terminal 1–95 amino acids of vimentin exclusively interact with the HCV envelope protein E1. Introducing either full‐length or head region of vimentin is capable of restoring the cell–cell transmission deficiency in vimentin‐knockout cells. Moreover, we showed that it is vimentin on the plasma membrane of recipient cells that orchestrates HCV cell–cell transmission. Consequently, vimentin antibody, either applied individually or in combination with HCV neutralizing antibody, exerts pronounced inhibition of HCV cell–cell transmission. Together, the results unveil an unrecognized function of vimentin as a unique venue dominating viral transmission, providing novel insights into propelling advancements in vimentin‐targeted anti‐HCV therapies.https://doi.org/10.1002/advs.202408917cell surface vimentincytoskeletal vimentinhepatitis C virusintermediate filamentsviral cell–cell transmission |
| spellingShingle | Yifan Xing Zeyu Wen Jie Mei Xinyi Huang Shuangshuang Zhao Jin Zhong Yaming Jiu Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus Advanced Science cell surface vimentin cytoskeletal vimentin hepatitis C virus intermediate filaments viral cell–cell transmission |
| title | Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus |
| title_full | Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus |
| title_fullStr | Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus |
| title_full_unstemmed | Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus |
| title_short | Cytoskeletal Vimentin Directs Cell‐Cell Transmission of Hepatitis C Virus |
| title_sort | cytoskeletal vimentin directs cell cell transmission of hepatitis c virus |
| topic | cell surface vimentin cytoskeletal vimentin hepatitis C virus intermediate filaments viral cell–cell transmission |
| url | https://doi.org/10.1002/advs.202408917 |
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