Selection pressure on the hepatitis B virus pre-S/S and P open reading frames in Tongan subjects with a chronic hepatitis B virus infection

作者：Abbott William G H^*; Tsai Peter; Ross Howard A; ' Ofanoa Malakai; Trevarton Alexander J; Hornell John; Munn Stephen R; Gane Edward J

来源：Antiviral Research, 2012, 96(2): 148-157.

DOI：10.1016/j.antiviral.2012.08.007

• Hepatitis B virus
• Phylogenetics
• HLA class I
• Polymerase gene
• Envelope gene
• HBeAg

Identification of the full repertoire of hepatitis B virus (HBV) peptides that are presented to CD8+ T cells by common HLA class I alleles will be useful for designing immunotherapies for chronic hepatitis B. One hundred and seventy five cloned sequences containing the pre-S/S and P open reading frames (ORF) of the HBV were obtained from serum HBV-DNA of HBeAg-positive (n = 4) and HBeAg-negative (inactive healthy carriers (IHC), n = 16) Tongan subjects with an inactive chronic HBV infection. In addition, 34 and 32 sequences were obtained 5.2 +/- 1.4 (mean +/- SD) years apart from eight subjects. PAML was used to identify codons in the pre-S/S and P ORFs that were under positive selection pressure (omega %26gt; 1). The number of non-synonymous substitutions in these codons was compared in IHC who were homozygous for either HLA-B(*)4001 (n = 9) or HLA-B(*)5602 (n = 7), and who were either positive (n = 6) or negative (n = 10) for HLA-A(*)02. 34 codons in the pre-S/S and 11 codons in the P ORFs were under positive selection pressure. There was a higher number of non-synonymous substitutions in these codons in HBeAg-negative versus HBeAg-positive subjects in the P (p = 0.02) but not the pre-S/S (p = 0.64) ORF. There was no association between any HLA class I allele and non-synonymous substitutions in these codons. There was no increase in positive selection pressure on the pre-S/S and P ORFs with time. In conclusion, we could not find HLA class I-restricted selection pressure on any pre-S/S or P ORF amino acid: raising the possibility that peptide-based immunotherapies for chronic hepatitis B may not require peptides from these ORFs.

• 出版日期2012-11