1887

Abstract

(HCV) is a major cause of chronic hepatitis worldwide. Studies of the early steps of HCV infection have been hampered by the lack of convenient or models. Although several cell-surface molecules that mediate the binding of HCV envelope proteins to target cells have been identified, mechanisms of viral entry into human hepatocytes are still poorly understood. Vesicular stomatitis virus/HCV pseudotyped viruses expressing the HCV envelope glycoproteins on the viral envelope were generated and it was found that their entry into human hepatocytes required co-expression of E1 and E2 on the pseudotype surface. Neutralization of pseudotype infection by anti-HCV antibodies suggested that cellular entry was mediated by HCV envelope glycoproteins and by previously characterized cell-surface molecules, including CD81. An entry assay based on the release of a fluorochrome from labelled HCV pseudotypes provided evidence for a pH-dependent fusion of the pseudotype envelope with a cellular compartment. By using a panel of endocytosis inhibitors, it is postulated that penetration of HCV into primary cultures of hepatocytes takes place by clathrin-mediated endocytosis.

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2006-09-01
2024-04-19
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