Comparison of envelope 2 CD81 binding regions in PBMC-derived versus serum-derived hepatitis C virus isolates: higher conservation of CD81 region 2 in PBMC isolates

J Viral Hepat. 2011 Mar;18(3):181-92. doi: 10.1111/j.1365-2893.2010.01296.x.

Abstract

The aim of the present study was to investigate the variability of hepatitis C virus (HCV) CD81 binding regions (CD81-1/2) in peripheral blood mononuclear cells (PBMC)-derived and serum-derived HCV-RNA samples. HCV-RNA was isolated from PBMC (10⁴ cells) and serum samples from 37 patients chronically infected with HCV genotype 1a/1b (n=21/16). The hypervariable regions 1/2 (amino acid 384-410, amino acid 474-482) and regions CD81-1/2 (amino acid 474-494, amino acid 522-551) were analysed. Mutational frequency of amino acid sequences was compared between PBMC-derived and serum-derived HCV variants as well as local accumulation of mutations. Furthermore, CD81 was quantified on PBMC. Mutational frequency was not different between PBMC-derived and serum-derived HCV variants. A trend to lower mutational frequency in genotype 1a PBMC variants compared with serum-derived variants was observed in region CD81-2 (5%vs 10%). Smoothed mutational frequency analysis showed a significantly lower variability within genotype 1a CD81-2 in PBMC-derived compared to serum-derived HCV-RNA (P=0.026). CD81 expression on PBMC was not correlated with the number of mutations within the CD81 binding regions.

Conclusion: A higher conservation was observed in region CD81-2 in PBMC-derived versus serum-derived HCV-RNA indicating selection of HCV variants on PBMC. The variability in the CD81 binding regions appeared to be independent from CD81 expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Female
  • Flow Cytometry
  • Genetic Variation
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepacivirus / metabolism
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Point Mutation
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Statistics, Nonparametric
  • Tetraspanin 28
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism

Substances

  • Antigens, CD
  • CD81 protein, human
  • RNA, Viral
  • Tetraspanin 28
  • Viral Envelope Proteins