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.
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.
Hofmann
Wolf Peter
WP
Innere Medizin II, Medizinische Klinik und Poliklinik, Universität des Saarlandes, Homburg, Germany.
Sarrazin
Christoph
C
Kronenberger
Bernd
B
Schönberger
Barbara
B
Bruch
Katharina
K
Zeuzem
Stefan
S
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
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