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    Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection


    Robinson, Mark W. and Aranday-Cortes, Elihu and Gatherer, Derek and Swann, Rachael and Liefhebber, Jolanda M. P. and Da Silva Filipe, Ana and Sigruener, Alex and Barclay, Stephen T. and Mills, Peter R. and Patel, Arvind H. and McLauchlan, John (2015) Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection. Liver International : Official Journal Of The International Association For The Study Of The Liver, 35 (10). ISSN 1478-3223

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    Abstract

    Background: Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy. Methods: To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls. Results: Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-a therapy. In contrast, genes controlled by IFN-c were induced in gt3-infected biopsies. Moreover, IFN-c levels were higher in gt3-infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes upregulated in gt3 infection were preferentially induced by IFN-c. The transcriptional profile of gt3 infection was unaffected by IFNL4 polymorphisms, providing a rationale for the reduced predictive power of IFNL genotyping in gt3-infected patients. Conclusions: The interactions between HCV genotypes 1 and 3 and hepatocytes are distinct. These unique interactions provide avenues to explore the biological mechanisms that drive viral genotype-specific differences in disease progression and treatment response. A greater understanding of the distinct host–pathogen interactions of the different HCV genotypes is required to facilitate optimal management of HCV infection.

    Item Type: Article
    Keywords: genotype; HCV; interferon; ISGs; transcriptomics;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12659
    Identification Number: https://doi.org/10.1111/liv.12830
    Depositing User: Mark Robinson
    Date Deposited: 30 Mar 2020 10:14
    Journal or Publication Title: Liver International : Official Journal Of The International Association For The Study Of The Liver
    Publisher: Wiley
    Refereed: Yes
    URI:

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