title: Mutations within the CD81-binding sites and hypervariable region 2 of the envelope 2 protein: correlation with treatment response in hepatitis C virus-infected patients.
abstract: The hepatitis C virus (HCV) envelope 2 (E2) protein interacts with the cellular receptor CD81 in vitro. Within E2, 2 CD81-binding sites were described. E2-CD81 interaction has been shown to modulate B and T cell function. The clinical importance of mutations within the CD81-binding sites and overlapping hypervariable region 2 (HVR2) in correlation with response to antiviral treatment is unknown. Fifty-five patients infected with HCV-1b or HCV-3a underwent interferon-alpha-based treatment. The E2 gene, comprising the CD81-binding sites and HVR2, was sequenced from pretreatment serum samples. The number of mutations within CD81-binding sites was not correlated with virologic treatment response in HCV-1b- and HCV-3a-infected patients. Within HVR2, the total number of mutations was significantly higher in HCV-1b-infected patients with a sustained response to interferon-alpha-based treatment (3.9; range, 1-6) than in those with relapse (2.9; range, 1-5) or those who did not respond (2.8; range, 1-5) (P = .041). However, when the same analyses were based only on functionally nonconserved mutations, no significant differences were observed.
authors.affiliation: Innere Medizin II, Medizinische Klinik und Poliklinik, Universität des Saarlandes, Homburg, Germany.
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Barbara
authors.initials: B
authors.lastname: Schönberger
authors.forename: Katharina
authors.initials: K
authors.lastname: Bruch
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D001665:Binding Sites; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011991:Receptors, Virus / Q000378:metabolism; D016415:Sequence Alignment; D060225:Tetraspanin 28; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D022801:Complementarity Determining Regions; D016898:Interferon-alpha; D008565:Membrane Proteins; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus