title: Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection.
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.
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.|School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
authors: Mark W
authors: MW
authors: Robinson
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
authors: Elihu
authors: E
authors: Aranday-Cortes
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.|Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
authors: Derek
authors: D
authors: Gatherer
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.|Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors: Rachael
authors: R
authors: Swann
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
authors: Jolanda M P
authors: JM
authors: Liefhebber
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
authors: Ana Da Silva
authors: Ada S
authors: Filipe
authors: Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Regensburg, Germany.
authors: Alex
authors: A
authors: Sigruener
authors: Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors: Stephen T
authors: ST
authors: Barclay
authors: Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors: Peter R
authors: PR
authors: Mills
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
authors: Arvind H
authors: AH
authors: Patel
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow, UK.
authors: John
authors: J
authors: McLauchlan
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics*; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014158:Transcription, Genetic; D059467:Transcriptome; D000095022:Interferon Lambda
chemical_list: D007371:Interferon-gamma; D007378:Interleukins; C573415:IFNG protein, human; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
keywords: HCV; ISGs; genotype; interferon; transcriptomics