title: Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication.
abstract: 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.
  
  
  METHODS
  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.
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France.
authors: Alexandre
authors: A
authors: Florimond
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France.
authors: Philippe
authors: P
authors: Chouteau
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France.
authors: Patrice
authors: P
authors: Bruscella
authors: Inserm U1085, Institut de Recherche Santé Environnement & Travail (IRSET), Rennes, France Université de Rennes 1, Rennes, France Fédération de Recherche BIOSIT de Rennes, UMS 3480-US18, Rennes, France.
authors: Jacques
authors: J
authors: Le Seyec
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France.
authors: Emilie
authors: E
authors: Mérour
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France.
authors: Nazim
authors: N
authors: Ahnou
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Créteil, France.
authors: Ariane
authors: A
authors: Mallat
authors: Centre de Recherche sur l'Inflammation, Inserm UMR 1149-Université Paris Diderot, Paris, France.
authors: Sophie
authors: S
authors: Lotersztajn
authors: Team 'Pathophysiology and Therapy of Chronic Viral Hepatitis', Inserm U955, Créteil, France Université Paris-Est, Créteil, France National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, Hôpital Henri Mondor, Créteil, France.
authors: Jean-Michel
authors: JM
authors: Pawlotsky
mesh_terms: D002460:Cell Line; D005838:Genotype; D016174:Hepacivirus / Q000472:pathogenicity*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000821:virology*; D006526:Hepatitis C / Q000235:genetics / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology*; D008156:Luciferases / Q000378:metabolism; D012093:Replicon / Q000235:genetics; D014771:Virion / Q000472:pathogenicity; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D008156:Luciferases
keywords: Fibrogenesis; Fibrosis; Hepatic Stellate Cell; Hepatitis C