{"title":"Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver.","authors":"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","doi":"10.3390/v16111743","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598975/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Viruses-Basel","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/v16111743","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.