Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways
Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been...
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| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2261556 |
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| author | Zhenyu Zhao Zhen Wei Jiaxin Zheng Zhihong Li Hecun Zou Xiang Wen Fahong Li Xueyu Wang Qian Huang Huaqing Zeng Hui Fan Xuefei Cai Jiming Zhang Bei Jia Ailong Huang Mengji Lu Yong Lin |
| author_facet | Zhenyu Zhao Zhen Wei Jiaxin Zheng Zhihong Li Hecun Zou Xiang Wen Fahong Li Xueyu Wang Qian Huang Huaqing Zeng Hui Fan Xuefei Cai Jiming Zhang Bei Jia Ailong Huang Mengji Lu Yong Lin |
| author_sort | Zhenyu Zhao |
| collection | DOAJ |
| description | Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) – late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment. |
| format | Article |
| id | doaj-art-81d600794b4c48c38d85bfc31e91d737 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-81d600794b4c48c38d85bfc31e91d7372025-08-20T03:28:48ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2261556Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathwaysZhenyu Zhao0Zhen Wei1Jiaxin Zheng2Zhihong Li3Hecun Zou4Xiang Wen5Fahong Li6Xueyu Wang7Qian Huang8Huaqing Zeng9Hui Fan10Xuefei Cai11Jiming Zhang12Bei Jia13Ailong Huang14Mengji Lu15Yong Lin16Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaDepartment of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaKey Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyKey Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Chongqing Medical University, Chongqing, People’s Republic of ChinaChronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) – late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment.https://www.tandfonline.com/doi/10.1080/22221751.2023.2261556Hepatitis B virusRAB5AautophagyendosomeVPS34 |
| spellingShingle | Zhenyu Zhao Zhen Wei Jiaxin Zheng Zhihong Li Hecun Zou Xiang Wen Fahong Li Xueyu Wang Qian Huang Huaqing Zeng Hui Fan Xuefei Cai Jiming Zhang Bei Jia Ailong Huang Mengji Lu Yong Lin Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways Emerging Microbes and Infections Hepatitis B virus RAB5A autophagy endosome VPS34 |
| title | Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways |
| title_full | Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways |
| title_fullStr | Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways |
| title_full_unstemmed | Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways |
| title_short | Hepatitis B virus promotes its own replication by enhancing RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways |
| title_sort | hepatitis b virus promotes its own replication by enhancing rab5a mediated dual activation of endosomal and autophagic vesicle pathways |
| topic | Hepatitis B virus RAB5A autophagy endosome VPS34 |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2261556 |
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