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

Robinson, M. W. et al. (2015) Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection. Liver International, 35(10), pp. 2256-2264. (doi:10.1111/liv.12830) (PMID:25800823) (PMCID:PMC4949513)

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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 IFNα therapy. In contrast, genes controlled by IFNγ were induced in gt3-infected biopsies. Moreover, IFNγ levels were higher in gt3 infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes up-regulated in gt3 infection were preferentially induced by IFNγ. 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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Swann, Rachael and Aranday-Cortes, Dr Elihu and Mills, Professor Peter and Da Silva Filipe, Dr Ana and Robinson, Dr Mark and Liefhebber, Dr Jolanda and Gatherer, Dr Derek and Patel, Professor Arvind and McLauchlan, Professor John
Authors: Robinson, M. W., Aranday-Cortes, E., Gatherer, D., Swann, R., Liefhebber, J. M. P., Da Silva Filipe, A., Sigruener, A., Barclay, S. T., Mills, P. R., Patel, A. H., and McLauchlan, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Liver International
Publisher:John Wiley & Sons, Inc.
ISSN:1478-3223
ISSN (Online):1478-3231
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Liver International 35(10): 2256-2264
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn MclauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH