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

J Infect Dis. 2003 Mar 15;187(6):982-7. doi: 10.1086/368221. Epub 2003 Mar 6.

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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Antiviral Agents / therapeutic use*
  • Binding Sites
  • Cloning, Molecular
  • Complementarity Determining Regions / metabolism
  • Female
  • Hepacivirus / genetics*
  • Hepacivirus / isolation & purification
  • Hepacivirus / metabolism
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Receptors, Virus / metabolism
  • Sequence Alignment
  • Tetraspanin 28
  • Treatment Outcome
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / metabolism

Substances

  • Antigens, CD
  • Antiviral Agents
  • CD81 protein, human
  • Complementarity Determining Regions
  • Interferon-alpha
  • Membrane Proteins
  • Receptors, Virus
  • Tetraspanin 28
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus

Associated data

  • GENBANK/AJ515607
  • GENBANK/AJ515608
  • GENBANK/AJ515609
  • GENBANK/AJ515610
  • GENBANK/AJ515611
  • GENBANK/AJ515612
  • GENBANK/AJ515613
  • GENBANK/AJ515614
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  • GENBANK/AJ515616
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  • GENBANK/AJ515619
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  • GENBANK/AJ515640
  • GENBANK/AJ515641
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  • GENBANK/AJ515644
  • GENBANK/AJ515645
  • GENBANK/AJ515646
  • GENBANK/AJ515647
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  • GENBANK/AJ515649
  • GENBANK/AJ515650
  • GENBANK/AJ515651
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  • GENBANK/AJ515653
  • GENBANK/AJ515654
  • GENBANK/AJ515655
  • GENBANK/AJ515656
  • GENBANK/AJ515657
  • GENBANK/AJ515658
  • GENBANK/AJ515659
  • GENBANK/AJ515660
  • GENBANK/AJ515661