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Liver Int. 2015 Oct;35(10):2256-64. doi: 10.1111/liv.12830. Epub 2015 Apr 7.

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

Author information

1
MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
2
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
3
Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
4
Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
5
Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Regensburg, Germany.
6
Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK.

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.

KEYWORDS:

HCV; ISGs; genotype; interferon; transcriptomics

PMID:
25800823
PMCID:
PMC4949513
DOI:
10.1111/liv.12830
[Indexed for MEDLINE]
Free PMC Article

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