A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change

Fengrong Ren, Asahito Tsubota, Takatsugu Hirokawa, Hiromitsu Kumada, Ziheng Yang, Hiroshi Tanaka

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in the 'a' determinant region, have been suggested to affect the antigenicity of the virus and the clinical outcome of the infected patient. However, no convincing evidence has been presented for this hypothesis, partly because the 3D structure of the S protein has not been determined. Comparative analysis of viral genes offers an approach to testing this hypothesis, as it may reveal signals of natural selection and provide insights into the functional significance of the observed amino acid substitutions. In this study, we analyze HBV S gene sequences obtained from 24 patients infected with HBV genotypes B or C, together with 16 representative viral strains of HBV genotypes A-F retrieved from GenBank. We use phylogenetic methods to infer evolutionary changes among HBV genotypes and to identify amino acid residues potentially under positive selective pressure. Furthermore, we employ the fragment assembly method to predict structural changes in the S protein. The results showed that an amino acid substitution within the 'a' determinant, T126I, was unique to genotype C, may affect the antigenicity of the HBsAg, and may result in poorer clinical outcomes of patients infected with genotype C viral strains. We suggest that an integrated approach of evolutionary comparison and structural prediction is useful in generating hypotheses for further laboratory validation.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalGene
Volume383
DOIs
Publication statusPublished - 2006 Nov 15

Keywords

  • 'a' determinant
  • 3D structure
  • Ancestral viral sequence
  • Chronic HBV infection
  • Clinical outcome
  • Positive selection

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change'. Together they form a unique fingerprint.

Cite this