‘Hbe minus’ mutants of hepatitis B virus. Molecular characterization and its relation to viral genotypes

The precore–core and S genes of HBV were directly sequenced from serum samples of 42 patients with chronic hepatitis B (16 hepatitis Be antigen [HBeAg]+and 26 anti-HBe+). Viral genotype A was identified in 12 cases, genotype D in 11 and genotype F in 19 cases. Precore mutations, mainly M1 (G1896A, stop at codon 28) were similarly found among viral genotypes A and D: seven cases (58%) and six cases (55%), respectively. The selection of M1 mutants from genotype D resulted in a more stable encapsidation signal but was less stable for genotype A precore mutants. Oddly enough, the encapsidation signal of M1 precore mutants from genotype F sequences were evenly distributed among less stable (genotype A M1 mutants) and more stable encapsidation signal (genotype D M1 mutants). This study shows that the selection of precore mutants that preclude the HBeAg expression, including the M1 mutation, does not necessarily depend on the stabilization of the encapsidation signal or the viral genotype In addition, the particular behavior of genotype F genomes at precore region is described.