Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus

Robinson, M.W., Swann, R. , Sigruener, A., Barclay, S.T., Mills, P.R., McLauchlan, J. and Patel, A. H. (2015) Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus. Journal of Viral Hepatitis, 22(4), pp. 384-390. (doi: 10.1111/jvh.12310) (PMID:25200131) (PMCID:PMC4409080)

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Abstract

Hepatitis C virus (HCV) can be classified into seven distinct genotypes that are associated with differing pathologies and respond differently to antiviral therapy. In the UK, genotype 1 and 3 are present in approximately equal proportions. Chronic infection with HCV genotype 3 is associated with increased liver steatosis and reduced peripheral total cholesterol levels, which potentially influences peripheral immune responses. To understand these differences, we investigated host gene transcription in peripheral blood mononuclear cells by microarray and quantitative PCR in patients with genotype 1 (n = 22) or genotype 3 infection (n = 22) and matched healthy controls (n = 15). Enrichment of genes involved in immune response and inflammatory pathways were present in patients infected with HCV genotype 1; however, no differences in genes involved in lipid or cholesterol metabolism were detected. This genotype-specific induction of genes is unrelated to IL28B genotype or previous treatment failure. Our data support the hypothesis that genotype 1 infection drives a skewed Type I interferon response and provides a foundation for future investigations into the host–pathogen interactions that underlie the genotype-specific clinical outcomes of chronic HCV infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robinson, Dr Mark and Swann, Dr Rachael and Patel, Professor Arvind and McLauchlan, Professor John
Authors: Robinson, M.W., Swann, R., Sigruener, A., Barclay, S.T., Mills, P.R., McLauchlan, J., and Patel, A. H.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Viral Hepatitis
Publisher:John Wiley & Sons Ltd.
ISSN:1352-0504
ISSN (Online):1365-2893
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Journal of Viral Hepatitis 22(4):384-390
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH