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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Female
  • Genotype
  • Hepatitis C / genetics*
  • Hepatitis C, Chronic / genetics*
  • Host-Pathogen Interactions
  • Humans
  • Interferon-gamma / metabolism
  • Interleukins / genetics*
  • Liver / pathology*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Transcription, Genetic
  • Transcriptome


  • IFNG protein, human
  • IFNL4 protein, human
  • Interleukins
  • Interferon-gamma