Unique surface gene variants of hepatitis B virus isolated from patients in the Philippines

Abstract

Point mutations and multiple variants across the "a" determinant can destroy the antigenicity and immunogenicity of hepatitis B virus (HBV) leading to false negative assay and vaccine escape. In this study, the presence of surface gene variants of HBV was investigated among patients clinically diagnosed with chronic hepatitis B and positive for HBV DNA from 2002 to 2009. Sequence analysis of the surface gene of HBV showed that 23 (43%) of the 53 isolates had variations. Out of the 23 isolates, 15 (65%) exhibited single or multiple substitutions, which resulted to specific amino acid changes. The remaining 8 (35%) isolates had silent mutations. The amino acid substitution M133T which was associated with failure of HBsAg detection was found in one isolate (7%, 1/15), while the amino acid substitution D144A which was associated with vaccine escape was observed in one isolate (7%, 1/15). No G145R mutation was observed. Of the 15 isolates with identified single or multiple substitutions, 6 (40%) were found to have unique sequences which caused changes in the hydrophobicity profile in the protein. Unique sequence variants at amino acid positions M103I, L109P, S117R, F134I, and S136L found in this study have not yet been reported. These data should be taken into account when developing next generation HBV assays to detect both common and unique variants, and when new HBV vaccines will be designed.

Keywords: genotype; hepatitis B virus; mutation; surface gene; variation; “a” determinant.