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Hepatitis C virus infection of cholangiocarcinoma cell lines

Fletcher, N. F., Humphreys, E., Jennings, E., Osburn, W., Lissauer, S., Wilson, G. K., van Ijzendoorn, S. C. D., Baumert, T. F., Balfe, P., Afford, S. & McKeating, J. A., Jun-2015, In : The Journal of general virology. 96, 6, p. 1380-1388 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Nicola F. Fletcher
  • Elizabeth Humphreys
  • Elliott Jennings
  • William Osburn
  • Samantha Lissauer
  • Garrick K. Wilson
  • Sven C. D. van Ijzendoorn
  • Thomas F. Baumert
  • Peter Balfe
  • Simon Afford
  • Jane A. McKeating

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.

Original languageEnglish
Pages (from-to)1380-1388
Number of pages9
JournalThe Journal of general virology
Volume96
Issue number6
Publication statusPublished - Jun-2015

    Keywords

  • INTRAHEPATIC CHOLANGIOCARCINOMA, RNA SEQUENCES, LIFE-CYCLE, HEPATOCYTES, LIVER, ENTRY, REPLICATION, CULTURE, TISSUE, PH

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