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Virus-Cell Interactions

Structure-Function Analysis of Hepatitis C Virus Envelope-CD81 Binding

Roberto Petracca, Fabiana Falugi, Giuliano Galli, Nathalie Norais, Domenico Rosa, Susanna Campagnoli, Vito Burgio, Enrico Di Stasio, Bruno Giardina, Michael Houghton, Sergio Abrignani, Guido Grandi
Roberto Petracca
Chiron Research Centre, 53100 Siena,
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Fabiana Falugi
Chiron Research Centre, 53100 Siena,
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Giuliano Galli
Chiron Research Centre, 53100 Siena,
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Nathalie Norais
Chiron Research Centre, 53100 Siena,
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Domenico Rosa
Chiron Research Centre, 53100 Siena,
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Susanna Campagnoli
Chiron Research Centre, 53100 Siena,
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Vito Burgio
Fondazione Andrea Cesalpino, c/o Istituto I Clinica Medica, Università La Sapienza, Policlinico Umberto I, 00161 Rome, and
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Enrico Di Stasio
Istituto di Fisica and
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Bruno Giardina
Istituto di Chimica e Chimica Clinica,Facoltà di Medicina e Chirurgia, UCSC, 00168 Rome, Italy, and
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Michael Houghton
Chiron Technologies, Emeryville, California 94608
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Sergio Abrignani
Chiron Research Centre, 53100 Siena,
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Guido Grandi
Chiron Research Centre, 53100 Siena,
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DOI: 10.1128/JVI.74.10.4824-4830.2000
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ABSTRACT

Hepatitis C virus (HCV) is a major human pathogen causing chronic liver disease. We have recently found that the large extracellular loop (LEL) of human CD81 binds HCV. This finding prompted us to assess the structure-function features of HCV-CD81 interaction by using recombinant E2 protein and a recombinant soluble form of CD81 LEL. We have found that HCV-E2 binds CD81 LEL with a Kd of 1.8 nM; CD81 can mediate attachment of E2 on hepatocytes; engagement of CD81 mediates internalization of only 30% of CD81 molecules even after 12 h; and the four cysteines of CD81 LEL form two disulfide bridges, the integrity of which is necessary for CD81-HCV interaction. Altogether our data suggest that neutralizing antibodies aimed at interfering with HCV binding to human cells should have an affinity higher than 10−9 M, that HCV binding to hepatocytes may not entirely depend on CD81, that CD81 is an attachment receptor with poor capacity to mediate virus entry, and that reducing environments do not favor CD81-HCV interaction. These studies provide a better understanding of the CD81-HCV interaction and should thus help to elucidate the viral life cycle and to develop new strategies aimed at interfering with HCV binding to human cells.

  • Copyright © 2000 American Society for Microbiology
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Structure-Function Analysis of Hepatitis C Virus Envelope-CD81 Binding
Roberto Petracca, Fabiana Falugi, Giuliano Galli, Nathalie Norais, Domenico Rosa, Susanna Campagnoli, Vito Burgio, Enrico Di Stasio, Bruno Giardina, Michael Houghton, Sergio Abrignani, Guido Grandi
Journal of Virology May 2000, 74 (10) 4824-4830; DOI: 10.1128/JVI.74.10.4824-4830.2000

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Structure-Function Analysis of Hepatitis C Virus Envelope-CD81 Binding
Roberto Petracca, Fabiana Falugi, Giuliano Galli, Nathalie Norais, Domenico Rosa, Susanna Campagnoli, Vito Burgio, Enrico Di Stasio, Bruno Giardina, Michael Houghton, Sergio Abrignani, Guido Grandi
Journal of Virology May 2000, 74 (10) 4824-4830; DOI: 10.1128/JVI.74.10.4824-4830.2000
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