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Elevated interferon‐stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus
Author(s) -
Robinson M. W.,
Swann R.,
Sigruener A.,
Barclay S. T.,
Mills P. R.,
McLauchlan J.,
Patel A. H.
Publication year - 2015
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12310
Subject(s) - genotype , biology , hepatitis c virus , immune system , peripheral blood mononuclear cell , immunology , interferon , virology , gene , virus , hepacivirus , microarray , gene expression , genetics , in vitro
Summary 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 IL 28B 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.