title: Transcriptome sequencing, microarray, and proteomic analyses reveal cellular and metabolic impact of hepatitis C virus infection in vitro.
abstract: Hepatitis C virus (HCV) is a major cause of liver disease but the full impact of HCV infection on the hepatocyte is poorly understood. RNA sequencing (RNA-Seq) is a novel method to analyze the full transcriptional activity of a cell or tissue, thus allowing new insight into the impact of HCV infection. We conducted the first full-genome RNA-Seq analysis in a host cell to analyze infected and noninfected cells, and compared this to microarray and proteomic analyses. The combined power of the triple approach revealed that HCV infection affects a number of previously unreported canonical pathways and biological functions, including pregnane X receptor/retinoic acid receptor activation as a potential host antiviral response, and integrin-linked kinase signaling as an entry factor. This approach also identified several mechanisms implicated in HCV pathogenesis, including an increase in reactive oxygen species. HCV infection had a broad effect on cellular metabolism, leading to increases in cellular cholesterol and free fatty acid levels, associated with a profound and specific decrease in cellular glucose levels.
  
  
  CONCLUSIONS
  RNA-Seq technology, especially when combined with established methods, demonstrated that HCV infection has potentially wide-ranging effects on cellular gene and protein expression. This in vitro study indicates a substantial metabolic impact of HCV infection and highlights new mechanisms of virus-host interaction which may be highly relevant to pathogenesis in vivo.
authors.affiliation: Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK. Stephen.woodhouse@bioch.ox.ac.uk
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Woodhouse
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Narayan
authors.forename: Sally
authors.initials: S
authors.lastname: Latham
authors.forename: Sheena
authors.initials: S
authors.lastname: Lee
authors.forename: Robin
authors.initials: R
authors.lastname: Antrobus
authors.forename: Bevin
authors.initials: B
authors.lastname: Gangadharan
authors.forename: Shujun
authors.initials: S
authors.lastname: Luo
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Nicole
authors.initials: N
authors.lastname: Zitzmann
mesh_terms: D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism*; D046228:Microarray Analysis; D020543:Proteome
chemical_list: D020543:Proteome