Interferon-alpha responsible EPN3 regulates hepatitis B virus replication
Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane prote...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.944489/full |
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| author | Xueqian Li Zhe Wang Zhe Wang Weiping Zhou Xuanhe Fu Yunpeng Zhang Ye Sun Biao Yang Yuxin Bai Chunwei Dai Xiaolun Xu Fan Cui Ying Zhao Yuping Zhang Bengang Wang Yingfang Li Masamichi Muramatsu Masamichi Muramatsu Kousho Wakae Guangyan Liu |
| author_facet | Xueqian Li Zhe Wang Zhe Wang Weiping Zhou Xuanhe Fu Yunpeng Zhang Ye Sun Biao Yang Yuxin Bai Chunwei Dai Xiaolun Xu Fan Cui Ying Zhao Yuping Zhang Bengang Wang Yingfang Li Masamichi Muramatsu Masamichi Muramatsu Kousho Wakae Guangyan Liu |
| author_sort | Xueqian Li |
| collection | DOAJ |
| description | Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed. |
| first_indexed | 2024-04-14T03:56:07Z |
| format | Article |
| id | doaj.art-322fd7c5f8d940e4ba03ca74ab9f5e58 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-14T03:56:07Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-322fd7c5f8d940e4ba03ca74ab9f5e582022-12-22T02:13:45ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-07-01910.3389/fmed.2022.944489944489Interferon-alpha responsible EPN3 regulates hepatitis B virus replicationXueqian Li0Zhe Wang1Zhe Wang2Weiping Zhou3Xuanhe Fu4Yunpeng Zhang5Ye Sun6Biao Yang7Yuxin Bai8Chunwei Dai9Xiaolun Xu10Fan Cui11Ying Zhao12Yuping Zhang13Bengang Wang14Yingfang Li15Masamichi Muramatsu16Masamichi Muramatsu17Kousho Wakae18Guangyan Liu19Department of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaDepartment of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, ChinaThe Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaDepartment of Immunology, Shenyang Medical College, Shenyang, ChinaDepartment of Pathophysiology, Shenyang Medical College, Shenyang, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaCollege of Basic Medical Sciences, Shenyang Medical College, Shenyang, ChinaDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaCollege of Basic Medical Sciences, Shenyang Medical College, Shenyang, ChinaCollege of Basic Medical Sciences, Shenyang Medical College, Shenyang, ChinaCollege of Basic Medical Sciences, Shenyang Medical College, Shenyang, ChinaDepartment of Hepatobiliary Surgery, Institute of General Surgery, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Virology II, National Institute of Infectious Disease, Tokyo, JapanDepartment of Virology II, National Institute of Infectious Disease, Tokyo, JapanFoundation for Biomedical Research and Innovation, Kobe, JapanDepartment of Virology II, National Institute of Infectious Disease, Tokyo, JapanDepartment of Pathogen Biology, Shenyang Medical College, Shenyang, ChinaHepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.https://www.frontiersin.org/articles/10.3389/fmed.2022.944489/fullEPN3HBVIFN-αp53AID |
| spellingShingle | Xueqian Li Zhe Wang Zhe Wang Weiping Zhou Xuanhe Fu Yunpeng Zhang Ye Sun Biao Yang Yuxin Bai Chunwei Dai Xiaolun Xu Fan Cui Ying Zhao Yuping Zhang Bengang Wang Yingfang Li Masamichi Muramatsu Masamichi Muramatsu Kousho Wakae Guangyan Liu Interferon-alpha responsible EPN3 regulates hepatitis B virus replication Frontiers in Medicine EPN3 HBV IFN-α p53 AID |
| title | Interferon-alpha responsible EPN3 regulates hepatitis B virus replication |
| title_full | Interferon-alpha responsible EPN3 regulates hepatitis B virus replication |
| title_fullStr | Interferon-alpha responsible EPN3 regulates hepatitis B virus replication |
| title_full_unstemmed | Interferon-alpha responsible EPN3 regulates hepatitis B virus replication |
| title_short | Interferon-alpha responsible EPN3 regulates hepatitis B virus replication |
| title_sort | interferon alpha responsible epn3 regulates hepatitis b virus replication |
| topic | EPN3 HBV IFN-α p53 AID |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.944489/full |
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