Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection
Background/Objectives: Hepatitis B virus (HBV) infection is a worldwide health problem responsible for chronic liver disease and hepatocellular carcinoma. Both innate immunity and the adaptive immune response play central roles in the development of chronic hepatitis and liver cancer. We previously...
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2025-04-01
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| author | Huarui Bao Masataka Tsuge Serami Murakami Yasutoshi Fujii Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka |
| author_facet | Huarui Bao Masataka Tsuge Serami Murakami Yasutoshi Fujii Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka |
| author_sort | Huarui Bao |
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| description | Background/Objectives: Hepatitis B virus (HBV) infection is a worldwide health problem responsible for chronic liver disease and hepatocellular carcinoma. Both innate immunity and the adaptive immune response play central roles in the development of chronic hepatitis and liver cancer. We previously performed a comprehensive analysis of gene expression in the livers of HBV-infected chimeric mice and found that several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were upregulated by HBV infection. However, due to the absence of adaptive immunity in uPA/SCID chimeric mice, we were unable to analyze the effect of the host immune response. Methods: In this study, we compared gene expression profiles in the livers obtained from HBV-infected chimeric mice with those of HBV carriers. Results: After HBV infection, the expression of genes associated with inflammation and immune response, especially involving the Th1 and Th2 activation pathways, was altered as HBV-specific intracellular immune responses both in vivo and in clinical samples. Interestingly, the proinflammatory gene IL12A was induced by HBV infection in the chimeric mouse livers but not in the human livers, and associated genes, such as SRDA5A2, AR, and CCR3, showed differential alteration by HBV infection between the chimeric mouse and human livers. Conclusions: These results suggest that hepatocarcinogenesis may be suppressed by host immunity in HBV carriers. This study highlights potential new implications for inhibiting the progression of HBV-related liver diseases, including hepatocarcinogenesis. |
| format | Article |
| id | doaj-art-e78623ee8ca84b99b5fa505b74edb329 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Livers |
| spelling | doaj-art-e78623ee8ca84b99b5fa505b74edb3292025-08-20T03:27:23ZengMDPI AGLivers2673-43892025-04-01521810.3390/livers5020018Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV InfectionHuarui Bao0Masataka Tsuge1Serami Murakami2Yasutoshi Fujii3Shinsuke Uchikawa4Hatsue Fujino5Atsushi Ono6Eisuke Murakami7Tomokazu Kawaoka8Daiki Miki9Clair Nelson Hayes10Shiro Oka11Department of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Hiroshima University, Hiroshima 734-8551, JapanBackground/Objectives: Hepatitis B virus (HBV) infection is a worldwide health problem responsible for chronic liver disease and hepatocellular carcinoma. Both innate immunity and the adaptive immune response play central roles in the development of chronic hepatitis and liver cancer. We previously performed a comprehensive analysis of gene expression in the livers of HBV-infected chimeric mice and found that several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were upregulated by HBV infection. However, due to the absence of adaptive immunity in uPA/SCID chimeric mice, we were unable to analyze the effect of the host immune response. Methods: In this study, we compared gene expression profiles in the livers obtained from HBV-infected chimeric mice with those of HBV carriers. Results: After HBV infection, the expression of genes associated with inflammation and immune response, especially involving the Th1 and Th2 activation pathways, was altered as HBV-specific intracellular immune responses both in vivo and in clinical samples. Interestingly, the proinflammatory gene IL12A was induced by HBV infection in the chimeric mouse livers but not in the human livers, and associated genes, such as SRDA5A2, AR, and CCR3, showed differential alteration by HBV infection between the chimeric mouse and human livers. Conclusions: These results suggest that hepatocarcinogenesis may be suppressed by host immunity in HBV carriers. This study highlights potential new implications for inhibiting the progression of HBV-related liver diseases, including hepatocarcinogenesis.https://www.mdpi.com/2673-4389/5/2/18hepatitis B virus (HBV)human hepatocytegene expressionnext-generation sequencingDEGsimmune response |
| spellingShingle | Huarui Bao Masataka Tsuge Serami Murakami Yasutoshi Fujii Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection Livers hepatitis B virus (HBV) human hepatocyte gene expression next-generation sequencing DEGs immune response |
| title | Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection |
| title_full | Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection |
| title_fullStr | Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection |
| title_full_unstemmed | Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection |
| title_short | Comparison of Differentially Expressed Genes in Human Versus in Chimeric Mouse Livers Following HBV Infection |
| title_sort | comparison of differentially expressed genes in human versus in chimeric mouse livers following hbv infection |
| topic | hepatitis B virus (HBV) human hepatocyte gene expression next-generation sequencing DEGs immune response |
| url | https://www.mdpi.com/2673-4389/5/2/18 |
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