Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy
Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2100831 |
| _version_ | 1811222599349305344 |
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| author | Ning Li Kangkang Yu Minhui Dong Jinyu Wang Feifei Yang Haoxiang Zhu Jie Yu Jingshu Yang Wentao Xie Bidisha Mitra Richeng Mao Feizhen Wu Haitao Guo Jiming Zhang |
| author_facet | Ning Li Kangkang Yu Minhui Dong Jinyu Wang Feifei Yang Haoxiang Zhu Jie Yu Jingshu Yang Wentao Xie Bidisha Mitra Richeng Mao Feizhen Wu Haitao Guo Jiming Zhang |
| author_sort | Ning Li |
| collection | DOAJ |
| description | Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy. |
| first_indexed | 2024-04-12T08:18:39Z |
| format | Article |
| id | doaj.art-34ac08a2fed74782886862be48e5288d |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-12T08:18:39Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-34ac08a2fed74782886862be48e5288d2022-12-22T03:40:41ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111876188910.1080/22221751.2022.2100831Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapyNing Li0Kangkang Yu1Minhui Dong2Jinyu Wang3Feifei Yang4Haoxiang Zhu5Jie Yu6Jingshu Yang7Wentao Xie8Bidisha Mitra9Richeng Mao10Feizhen Wu11Haitao Guo12Jiming Zhang13Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCancer Virology Program, UPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USADepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaLaboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of ChinaCancer Virology Program, UPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USADepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaChronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.https://www.tandfonline.com/doi/10.1080/22221751.2022.2100831Chronic hepatitis Binterferon therapyliver biopsytranscriptomeHBeAg |
| spellingShingle | Ning Li Kangkang Yu Minhui Dong Jinyu Wang Feifei Yang Haoxiang Zhu Jie Yu Jingshu Yang Wentao Xie Bidisha Mitra Richeng Mao Feizhen Wu Haitao Guo Jiming Zhang Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy Emerging Microbes and Infections Chronic hepatitis B interferon therapy liver biopsy transcriptome HBeAg |
| title | Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy |
| title_full | Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy |
| title_fullStr | Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy |
| title_full_unstemmed | Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy |
| title_short | Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy |
| title_sort | intrahepatic transcriptomics reveals gene signatures in chronic hepatitis b patients responded to interferon therapy |
| topic | Chronic hepatitis B interferon therapy liver biopsy transcriptome HBeAg |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2100831 |
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