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Animal: RNA Viruses |
MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK1
US Military HIV Research Program, Rockville, MD, USA2
University of Reading, School of Animal & Microbial Sciences, PO Box 228, Reading, UK3
Author for correspondence: Arvind Patel. Fax +44 141 337 2236. e-mail a.patel{at}vir.gla.ac.uk
Structure–function analysis of the hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, has been difficult due to the unavailability of HCV virions. Truncated soluble forms of E2 have been used as models to study virus interaction with the putative HCV receptor CD81, but they may not fully mimic E2 structures on the virion. Here, we compared the CD81-binding characteristics of truncated E2 (E2660) and full-length (FL) E1E2 complex expressed in mammalian cells, and of HCV virus-like particles (VLPs) generated in insect cells. All three glycoprotein forms interacted with human CD81 in an in vitro binding assay, allowing us to test a panel of well-characterized anti-E2 monoclonal antibodies (MAbs) for their ability to inhibit the glycoprotein–CD81 interaction. MAbs specific for E2 amino acid (aa) regions 396–407, 412–423 and 528–535 blocked binding to CD81 of all antigens tested. However, MAbs specific for regions 432–443, 436–443 and 436–447 inhibited the interaction of VLPs, but not of E2660 or the FL E1E2 complex with CD81, indicating the existence of structural differences amongst the E2 forms. These findings underscore the need to carefully select an appropriate ligand for structure–function analysis.
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B. Bartosch, A. Vitelli, C. Granier, C. Goujon, J. Dubuisson, S. Pascale, E. Scarselli, R. Cortese, A. Nicosia, and F.-L. Cosset Cell Entry of Hepatitis C Virus Requires a Set of Co-receptors That Include the CD81 Tetraspanin and the SR-B1 Scavenger Receptor J. Biol. Chem., October 24, 2003; 278(43): 41624 - 41630. [Abstract] [Full Text] [PDF]
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L. Cocquerel, C.-C. Kuo, J. Dubuisson, and S. Levy CD81-Dependent Binding of Hepatitis C Virus E1E2 Heterodimers J. Virol., October 1, 2003; 77(19): 10677 - 10683. [Abstract] [Full Text] [PDF]
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 B. Bartosch, J. Dubuisson, and F.-L. Cosset Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1-E2 Envelope Protein Complexes J. Exp. Med., March 3, 2003; 197(5): 633 - 642. [Abstract] [Full Text] [PDF]
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R. Roccasecca, H. Ansuini, A. Vitelli, A. Meola, E. Scarselli, S. Acali, M. Pezzanera, B. B. Ercole, J. McKeating, A. Yagnik, et al. Binding of the Hepatitis C Virus E2 Glycoprotein to CD81 Is Strain Specific and Is Modulated by a Complex Interplay between Hypervariable Regions 1 and 2 J. Virol., February 1, 2003; 77(3): 1856 - 1867. [Abstract] [Full Text] [PDF]
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L. Cocquerel, E. R. Quinn, M. Flint, K. G. Hadlock, S. K. H. Foung, and S. Levy Recognition of Native Hepatitis C Virus E1E2 Heterodimers by a Human Monoclonal Antibody J. Virol., December 20, 2002; 77(2): 1604 - 1609. [Abstract] [Full Text] [PDF]
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B. Saunier, M. Triyatni, L. Ulianich, P. Maruvada, P. Yen, and L. D. Kohn Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes J. Virol., December 6, 2002; 77(1): 546 - 559. [Abstract] [Full Text] [PDF]
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H. E. Drummer, K. A. Wilson, and P. Poumbourios Identification of the Hepatitis C Virus E2 Glycoprotein Binding Site on the Large Extracellular Loop of CD81 J. Virol., October 2, 2002; 76(21): 11143 - 11147. [Abstract] [Full Text] [PDF]
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M. Triyatni, B. Saunier, P. Maruvada, A. R. Davis, L. Ulianich, T. Heller, A. Patel, L. D. Kohn, and T. J. Liang Interaction of Hepatitis C Virus-Like Particles and Cells: a Model System for Studying Viral Binding and Entry J. Virol., August 12, 2002; 76(18): 9335 - 9344. [Abstract] [Full Text] [PDF]
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R. F. Clayton, A. Owsianka, J. Aitken, S. Graham, D. Bhella, and A. H. Patel Analysis of Antigenicity and Topology of E2 Glycoprotein Present on Recombinant Hepatitis C Virus-Like Particles J. Virol., June 27, 2002; 76(15): 7672 - 7682. [Abstract] [Full Text] [PDF]
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M. Lambot, S. Fretier, A. O. De Beeck, B. Quatannens, S. Lestavel, V. Clavey, and J. Dubuisson Reconstitution of Hepatitis C Virus Envelope Glycoproteins into Liposomes as a Surrogate Model to Study Virus Attachment J. Biol. Chem., May 31, 2002; 277(23): 20625 - 20630. [Abstract] [Full Text] [PDF]
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K. Meyer, A. Basu, C. T. Przysiecki, L. M. Lagging, A. M. Di Bisceglie, A. J. Conley, and R. Ray Complement-Mediated Enhancement of Antibody Function for Neutralization of Pseudotype Virus Containing Hepatitis C Virus E2 Chimeric Glycoprotein J. Virol., March 1, 2002; 76(5): 2150 - 2158. [Abstract] [Full Text] [PDF]
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