TY - JOUR
T1 - Hepatitis C virus infection of cholangiocarcinoma cell lines
AU - Fletcher, Nicola F.
AU - Humphreys, Elizabeth
AU - Jennings, Elliott
AU - Osburn, William
AU - Lissauer, Samantha
AU - Wilson, Garrick K.
AU - van IJzendoorn, Sven C.D.
AU - Baumert, Thomas F.
AU - Balfe, Peter
AU - Afford, Simon
AU - McKeating, Jane A.
N1 - Publisher Copyright:
© 2015 The Author.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84937570275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937570275&partnerID=8YFLogxK
U2 - 10.1099/vir.0.000090
DO - 10.1099/vir.0.000090
M3 - Article
C2 - 25701818
AN - SCOPUS:84937570275
SN - 0022-1317
VL - 96
SP - 1380
EP - 1388
JO - Journal of General Virology
JF - Journal of General Virology
ER -