title: Hepatitis C virus infection of cholangiocarcinoma cell lines.
abstract: Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV replication and contribute to the hepatic reservoir. We screened cholangiocytes along with a panel of cholangiocarcinoma-derived cell lines for their ability to support HCV entry and replication. While primary cholangiocytes were refractory to infection and lacked expression of several entry factors, two cholangiocarcinoma lines, CC-LP-1 and Sk-ChA-1, supported efficient HCV entry; furthermore, Sk-ChA-1 cells supported full virus replication. In vivo cholangiocarcinomas expressed all of the essential HCV entry factors; however, cholangiocytes adjacent to the tumour and in normal tissue showed a similar pattern of receptor expression to ex vivo isolated cholangiocytes, lacking SR-BI expression, explaining their inability to support infection. This study provides the first report that HCV can infect cholangiocarcinoma cells and suggests that these heterogeneous tumours may provide a reservoir for HCV replication in vivo.
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Nicola F
authors.initials: NF
authors.lastname: Fletcher
authors.affiliation: Centre for Liver Research, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Elliott
authors.initials: E
authors.lastname: Jennings
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: William
authors.initials: W
authors.lastname: Osburn
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Lissauer
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Garrick K
authors.initials: GK
authors.lastname: Wilson
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen 9713AV, The Netherlands.
authors.forename: Sven C D
authors.initials: SCD
authors.lastname: van IJzendoorn
authors.affiliation: Inserm U1110, University of Strasbourg 3 Rue Koeberlé, F-67000 Strasbourg, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Balfe
authors.affiliation: Centre for Liver Research, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Afford
authors.affiliation: Centre for Liver Research, University of Birmingham, Birmingham B15 2TT, UK.|Centre for Human Virology, Viral Hepatitis Laboratory, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000821:virology*; D016174:Hepacivirus / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D056189:Viral Tropism; D053586:Virus Internalization; D014779:Virus Replication