TY - JOUR
T1 - A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change
AU - Ren, Fengrong
AU - Tsubota, Asahito
AU - Hirokawa, Takatsugu
AU - Kumada, Hiromitsu
AU - Yang, Ziheng
AU - Tanaka, Hiroshi
N1 - Funding Information:
This study is supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to F.R. and H.T.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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.
AB - 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.
KW - 'a' determinant
KW - 3D structure
KW - Ancestral viral sequence
KW - Chronic HBV infection
KW - Clinical outcome
KW - Positive selection
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U2 - 10.1016/j.gene.2006.07.018
DO - 10.1016/j.gene.2006.07.018
M3 - Article
C2 - 16963200
AN - SCOPUS:33750081785
SN - 0378-1119
VL - 383
SP - 43
EP - 51
JO - Gene
JF - Gene
ER -
