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Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection
Author(s) -
Robinson Mark W.,
ArandayCortes Elihu,
Gatherer Derek,
Swann Rachael,
Liefhebber Jolanda M. P.,
Filipe Ana Da Silva,
Sigruener Alex,
Barclay Stephen T.,
Mills Peter R.,
Patel Arvind H.,
McLauchlan John
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12830
Subject(s) - genotype , biology , virology , hepatitis c virus , liver disease , immunology , gene , viral load , genotyping , virus , interferon , chronic infection , genetics , immune system , biochemistry
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 IFNL 4 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.