Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver
Cross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before an...
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2024-11-01
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| author | Huarui Bao Serami Murakami Masataka Tsuge Takuro Uchida Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka |
| author_facet | Huarui Bao Serami Murakami Masataka Tsuge Takuro Uchida Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka |
| author_sort | Huarui Bao |
| collection | DOAJ |
| description | Cross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before and after antiviral therapy (AVT) with entecavir and pegylated interferon, and then performed a comparative transcriptome analysis of gene expression alteration. After HBV infection, the expression of genes involved in multiple pathways was significantly altered in the HBV-infected livers. After AVT, the levels of 37 out of 89 genes downregulated by HBV infection were restored, and 54 of 157 genes upregulated by HBV infection were suppressed. Interestingly, genes associated with hypoxia and KRAS signaling were included among the 54 genes upregulated by HBV infection and downregulated by AVT. Several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were significantly downregulated by AVT, with a potential application for the suppression of hepato-carcinogenesis. |
| format | Article |
| id | doaj-art-db9d4583c1d0406e82acc1a95c231483 |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-db9d4583c1d0406e82acc1a95c2314832024-11-26T18:25:30ZengMDPI AGViruses1999-49152024-11-011611174310.3390/v16111743Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse LiverHuarui Bao0Serami Murakami1Masataka Tsuge2Takuro Uchida3Shinsuke Uchikawa4Hatsue Fujino5Atsushi Ono6Eisuke Murakami7Tomokazu Kawaoka8Daiki Miki9Clair Nelson Hayes10Shiro Oka11Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDivision of Travel Medicine and Health, Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University, Oita 879-5593, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanCross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before and after antiviral therapy (AVT) with entecavir and pegylated interferon, and then performed a comparative transcriptome analysis of gene expression alteration. After HBV infection, the expression of genes involved in multiple pathways was significantly altered in the HBV-infected livers. After AVT, the levels of 37 out of 89 genes downregulated by HBV infection were restored, and 54 of 157 genes upregulated by HBV infection were suppressed. Interestingly, genes associated with hypoxia and KRAS signaling were included among the 54 genes upregulated by HBV infection and downregulated by AVT. Several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were significantly downregulated by AVT, with a potential application for the suppression of hepato-carcinogenesis.https://www.mdpi.com/1999-4915/16/11/1743hepatitis B virusantiviral therapyhuman hepatocytegene expressionnext-generation sequencing |
| spellingShingle | Huarui Bao Serami Murakami Masataka Tsuge Takuro Uchida Shinsuke Uchikawa Hatsue Fujino Atsushi Ono Eisuke Murakami Tomokazu Kawaoka Daiki Miki Clair Nelson Hayes Shiro Oka Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver Viruses hepatitis B virus antiviral therapy human hepatocyte gene expression next-generation sequencing |
| title | Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver |
| title_full | Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver |
| title_fullStr | Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver |
| title_full_unstemmed | Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver |
| title_short | Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver |
| title_sort | alteration of gene expression after entecavir and pegylated interferon therapy in hbv infected chimeric mouse liver |
| topic | hepatitis B virus antiviral therapy human hepatocyte gene expression next-generation sequencing |
| url | https://www.mdpi.com/1999-4915/16/11/1743 |
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