HEPATITIS-B VIRUS-INFECTION - PRECORE MUTANTS AND ITS RELATION TO VIRAL GENOTYPES AND CORE MUTATIONS

The precore-core gene of hepatitis B virus (HBV) was directly sequence d from serum samples of 42 patients with chronic B hepatitis (19 hepat itis B e antigen [HBeAg]+ and 23 anti-HBe+), Viral genotypes were dete rmined by comparison with 11 reference sequences and by restriction an alysis, Genotype A was identified in 16 cases, genotype D in 24 cases, and other genotypes in 2 cases, Precore mutations, mainly M1 (stop at codon 28), were differently distributed among the viral genotypes: 3 cases (18.8%) with genotype A and 18 cases (75%) with genotype D, In s equences with precore mutants, the encapsidation signal was more stabl e (negative stabilization energy) than in sequences without precore mu tants, In genotype A, the M1 mutation coexisted with a second mutation (C --> T at position 1858 in codon 15), and both mutations were paire d in the secondary structure of the RNA encapsidation signal, which ju stified the rare presence of precore mutants in this genotype, The ana lysis showed different distribution of mutations depending on the vira l genotype; patients with genotype D were more likely to have persiste nt HBV infection by selection of precore mutants, Multiple amino acid substitutions were detected in the core region, mainly in two subseque nces that have been previously described as epitopes (flanked by codon s 11 to 27 and 74 to 83); the presence of these mutations was signific antly related to the presence of precore variants which abolished the expression of HBeAg. The study of viral genotypes in chronic HBV infec tion may be valuable in predicting the persistence of viral replicatio n after seroconversion to anti-HBe and suggest that the outcome of chr onic infection may be affected by the HBV variability.