Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to Anti-HBe

Hepatitis B virus (HBV) strains from anti-HBe positive patients often show specific mutations in the precore gene, the core promoter region, or both. The dynamics of seroconversion in relation to the appearance of these mutat ions has not been studied and compared between defined HBV genotypes. Sampl es from patients followed during seroconversion from HBeAg to anti-HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Amo ng 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to geno type B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotype s B, C and E showed changes in the core promoter, precore codon 28 or both, genotype A and D strains displayed a different pattern. In 4 of 6 anti-HBe positive samples from genotype A, the precore had a wild-type sequence whi le the core promoter sequence showed a specific TGA mutation. In another ge notype A strain a precore stop mutation was preceded by a mutation in codon 15, thus conserving base-pairing at the pregenomic RNA level in this regio n. In contrast, all genotype D strains showed wild-type sequences in both t he core promoter and precore codon 28 in pre- and post-seroconversion sampl es. Thus, in 8 patients with a mean follow up time of 17 months, wild-type sequences in both the core promoter and precore codon 28 were found after s eroconversion to anti-HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion. J. Mad. Virol. 60:107-112, 2000. (C) 2000 Wiley-Liss, Inc.