RT Journal Article
SR Electronic
T1 Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 957
OP 965
DO 10.1136/gutjnl-2013-305634
VO 64
IS 6
A1 Alexandre Florimond
A1 Philippe Chouteau
A1 Patrice Bruscella
A1 Jacques Le Seyec
A1 Emilie Mérour
A1 Nazim Ahnou
A1 Ariane Mallat
A1 Sophie Lotersztajn
A1 Jean-Michel Pawlotsky
YR 2015
UL http://gut.bmj.com/content/64/6/957.abstract
AB Background Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. Objective To assess whether human HSCs are susceptible to HCV infection. Design We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. Results In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. Conclusions Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.