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 Filipe, Ana Da Silva 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, 35 (10). pp. 2256-2264. 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-α therapy. In contrast, genes controlled by IFN-γ were induced in gt3-infected biopsies. Moreover, IFN-γ 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-γ. 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:
Journal Article
Journal or Publication Title:
Liver International
Additional Information:
© 2015 The Authors. Liver International Published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2721
Subjects:
ID Code:
73678
Deposited By:
Deposited On:
18 Jun 2015 05:40
Refereed?:
Yes
Published?:
Published
Last Modified:
27 Sep 2020 02:26