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Journal of Virology, June 2001, p. 5703-5710, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5703-5710.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Conservation of the Conformation and Positive Charges of Hepatitis C Virus E2 Envelope Glycoprotein Hypervariable Region 1 Points to a Role in Cell Attachment

François Penin,1,* Christophe Combet,1 Georgios Germanidis,2,dagger Pierre-Olivier Frainais,2 Gilbert Deléage,1 and Jean-Michel Pawlotsky2

Institut de Biologie et Chimie des Protéines, CNRS-UMR 5086, 69367 Lyon,1 and Department of Bacteriology and Virology and INSERM U99, Hôpital Henri Mondor, Université Paris XII, 94010 Créteil,2 France

Received 7 November 2000/Accepted 28 March 2001

Chronic hepatitis C virus (HCV) infection is a major cause of liver disease. The HCV polyprotein contains a hypervariable region (HVR1) located at the N terminus of the second envelope glycoprotein E2. The strong variability of this 27-amino-acid region is due to its apparent tolerance of amino acid substitutions together with strong selection pressures exerted by anti-HCV immune responses. No specific function has so far been attributed to HVR1. However, its presence at the surface of the viral particle suggests that it might be involved in viral entry. This would imply that HVR1 is not randomly variable. We sequenced 460 HVR1 clones isolated at various times from six HCV-infected patients receiving alpha interferon therapy (which exerts strong pressure towards quasispecies genetic evolution) and analyzed their amino acid sequences together with those of 1,382 nonredundant HVR1 sequences collected from the EMBL database. We found that (i) despite strong amino acid sequence variability related to strong pressures towards change, the chemicophysical properties and conformation of HVR1 were highly conserved, and (ii) HVR1 is a globally basic stretch, with the basic residues located at specific sequence positions. This conservation of positively charged residues indicates that HVR1 is involved in interactions with negatively charged molecules such as lipids, proteins, or glycosaminoglycans (GAGs). As with many other viruses, possible interaction with GAGs probably plays a role in host cell recognition and attachment.

* Corresponding author. Mailing address: IBCP-CNRS, 7 Passage du Vercors, 69367 Lyon Cedex 07, France. Phone: 33 (4) 72722648. Fax: 33 (4) 72722604. E-mail: f.penin{at}ibcp.fr.

dagger Present address: First Department of Medicine, Papageorgiou General Hospital, Thessaloniki 564-29, Greece.

Journal of Virology, June 2001, p. 5703-5710, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5703-5710.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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