title: Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment.
abstract: 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.
authors.affiliation: Institut de Biologie et Chimie des Protéines, CNRS-UMR 5086, 69367 Lyon, France. f. penin@ibcp.fr
authors.forename: F
authors.initials: F
authors.lastname: Penin
authors.forename: C
authors.initials: C
authors.lastname: Combet
authors.forename: G
authors.initials: G
authors.lastname: Germanidis
authors.forename: P O
authors.initials: PO
authors.lastname: Frainais
authors.forename: G
authors.initials: G
authors.lastname: Deléage
authors.forename: J M
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus; D007371:Interferon-gamma