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Journal of Virology, January 2008, p. 569-574, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01443-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Sonia Molina,1,8,{dagger} Valerie Castet,1,{dagger} Lydiane Pichard-Garcia,1 Czeslaw Wychowski,2 Eliane Meurs,3 Jean-Marc Pascussi,1 Camille Sureau,4 Jean-Michel Fabre,1,5 Antonio SaCunha,6 Dominique Larrey,1,7 Jean Dubuisson,2 Joliette Coste,1,8 Jane McKeating,9 Patrick Maurel,1* and Chantal Fournier-Wirth1,8

Inserm, U632, 34293 Montpellier, France; Univ. Montpellier 1, EA3768, 34000 Montpellier, France,1 CNRS, UPR2511, Unité Hépatite C, Institut de Biologie de Lille & Institut Pasteur de Lille, 59021 Lille, France,2 Institut Pasteur, Unité Hepacivirus, 75724 Paris, France,3 Institut National de Transfusion Sanguine, 75139 Paris, France,4 Hôpital Saint Eloi, Service de Chirurgie Digestive II, 34095 Montpellier, France,5 Hôpital Haut Lévèque, Service de Chirurgie Digestive, 33075 Pessac, France,6 Hôpital Saint Eloi, Service d'Hépatogastroentérologie, 34095 Montpellier, France,7 Etablissement Français du Sang, 34094 Montpellier, France,8 Division of Immunology and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom9

Received 3 July 2007/ Accepted 4 October 2007

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.

* Corresponding author. Mailing address: Inserm U632, Hepatic Physiopathology, 1919 route de Mende, 34293 Montpellier, Cedex 5, France. Phone: (33) 4 67 61 33 63. Fax: (33) 4 67 52 36 81. E-mail: maurel{at}montp.inserm.fr

{triangledown} Published ahead of print on 17 October 2007.

{dagger} These two authors contributed equally to this work.

Journal of Virology, January 2008, p. 569-574, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01443-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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