Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent |
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Authors: | Molina Sonia Castet Valerie Pichard-Garcia Lydiane Wychowski Czeslaw Meurs Eliane Pascussi Jean-Marc Sureau Camille Fabre Jean-Michel Sacunha Antonio Larrey Dominique Dubuisson Jean Coste Joliette McKeating Jane Maurel Patrick Fournier-Wirth Chantal |
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Institution: | Inserm U632, Hepatic Physiopathology, 1919 route de Mende, 34293 Montpellier, Cedex 5, France. |
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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. |
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