Abstract B96: Phylogenetic relatedness and novel mutations in the whole genomes of genotype A (subgenotype A1) of HBV isolates from a north Indian population

Abstract

Abstract Hepatitis B virus (HBV) has been classified into eight genotypes (A to H). The predominant genotypes in India are genotype D followed by genotype A and C. Our laboratory has first time reported genotypes E and F in India. In the present study, whole genome (approximately 3.2 kb long) was amplified from five chronic HBV patients, who are HBeAg negative and having nearly normal ALT/AST levels. The samples were sequenced to complete length and sequences were compared to wild type sequences from database. Phylogenetic analysis shows high degree of closeness of our strains with Philippines and eastern Indian strains. Our study confirmed 33–35 point mutations out of already reported 38 subgenotype A1 specific point mutations and which are distributed throughout the genome including enhancer I–X promoter, enhancer II-Core promoter, encapsidation signal, S1 and S2 promoter regions etc. In addition to this, novel Kozak sequence mutations like CCTT at positions 1809/10/11/1812 in place of regular TCAT sequence were also observed. This region comprises the Enhancer II-Core promoter region and mutations of this region results in decreased production of HBeAg. 1041G was present in place of 1041T in Enhancer I–X promoter region. It has been observed that Genotype A has G1896A mutation when preceded by a C1858T mutation, thus conserving the structural stability of the encapsidation signal. One sample shows the presence of 1858T with 1896G mutation, which results in weakness of structural stability of encapsidation signal. In addition, our samples show presence of 1862T which is a missense mutation and responsible for val to leu/phe amino acid substitution. This mutation is responsible for low production of HBeAg protein and found mainly in HBeAg negative patient. Samples also showed the deletion at 19 novel sites and addition at 5 novel sites when compared with the whole genome from database. The significance of these deletion and addition mutations and their effects on the disease progression to hepatocellularcarcinoma is active area of research in our laboratory. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B96.