Serum-Derived Hepatitis C Virus Infection of Primary Human Hepatocytes Is Tetraspanin CD81 Dependent

Author:

Molina Sonia12,Castet Valerie1,Pichard-Garcia Lydiane1,Wychowski Czeslaw3,Meurs Eliane4,Pascussi Jean-Marc1,Sureau Camille5,Fabre Jean-Michel16,SaCunha Antonio7,Larrey Dominique18,Dubuisson Jean3,Coste Joliette12,McKeating Jane9,Maurel Patrick1,Fournier-Wirth Chantal12

Affiliation:

1. Inserm, U632, 34293 Montpellier, France; Univ. Montpellier 1, EA3768, 34000 Montpellier, France

2. Etablissement Français du Sang, 34094 Montpellier, France

3. CNRS, UPR2511, Unité Hépatite C, Institut de Biologie de Lille & Institut Pasteur de Lille, 59021 Lille, France

4. Institut Pasteur, Unité Hepacivirus, 75724 Paris, France

5. Institut National de Transfusion Sanguine, 75139 Paris, France

6. Hôpital Saint Eloi, Service de Chirurgie Digestive II, 34095 Montpellier, France

7. Hôpital Haut Lévèque, Service de Chirurgie Digestive, 33075 Pessac, France

8. Hôpital Saint Eloi, Service d'Hépatogastroentérologie, 34095 Montpellier, France

9. Division of Immunology and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom

Abstract

ABSTRACT Hepatitis C virus-positive serum (HCVser, genotypes 1a to 3a) or HCV cell culture (JFH1/HCVcc) infection of primary normal human hepatocytes was assessed by measuring intracellular HCV RNA strands. Anti-CD81 antibodies and siRNA-CD81 silencing markedly inhibited (>90%) HCVser infection irrespective of HCV genotype, viral load, or liver donor, while hCD81-large intracellular loop (LEL) had no effect. However, JFH1/HCVcc infection of hepatocytes was modestly inhibited (40 to 60%) by both hCD81-LEL and anti-CD81 antibodies. In conclusion, CD81 is involved in HCVser infection of human hepatocytes, and comparative studies of HCVser versus JFH1/HCVcc infection of human hepatocytes and Huh-7.5 cells revealed that the cell-virion combination is determinant of the entry process.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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