Hepatitis C virus infection of cholangiocarcinoma cell lines

Research output: Contribution to journalArticle

Colleges, School and Institutes

External organisations

  • Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD
  • Department of Cell Biology; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
  • Inserm U1110, University of Strasbourg

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 tumor 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 tumors may provide a reservoir for HCV replication in vivo.

Details

Original languageEnglish
Pages (from-to)1380-1388
Number of pages8
JournalJournal of General Virology
Volume96
Issue number6
Early online date20 Feb 2015
Publication statusPublished - Jun 2015