Hepatitis B virus strains in Thailand: genomic variants in chronic carriers

Genetic heterogeneity of the hepatitis B virus (HBV) has been shown to influence the serological pattern and clinical picture in HBV infection. Thailand has a high transmission rate of HBV, but the molecular epidemiology of HBV strains circulating in this region was hitherto unknown. In this study, the HBV strains from 34 Thai HBsAg-positive patients were investigated. In a proportion of these samples, an antigenically important region of the S gene (n = 18), and the pre-S2 and precore genes (n = 15) were sequenced after PCR amplification. Four strains had in-frame deletions of an upstream region of the pre-S2 gene, with all deletions ending at the same nucleotide. In one of three anti-HBe positive strains without a translational stop at codon 28 of the precore gene, there was a one nucleotide insertion in the precore gene. This insertion would cause a frame shift and result in a nonsense protein being expressed, thus providing one explanation for the lack of HBeAg in this patient. Several rare or unique amino acid changes in the region between residues 120 and 161 of the S protein were found. Glycine 145 was changed to alanine in one strain, and this position showed an apparent mixture of glycine and arginine in another. In total, 10 strains displayed unexpected changes that were not related to the normal variability between subtypes or genetic subgroups. It is concluded that there is considerable heterogeneity in HBV strains in Thailand and that this could have clinical and epidemiological importance in a region with high HBV transmission rates.