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Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to anti‐HBe
Author(s) -
Bläckberg Jonas,
KiddLjunggren Karin
Publication year - 2000
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(200002)60:2<107::aid-jmv1>3.0.co;2-t
Subject(s) - genotype , virology , hbeag , seroconversion , hepatitis b virus , biology , promoter , orthohepadnavirus , hepadnaviridae , genetics , microbiology and biotechnology , virus , gene , hbsag , gene expression
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 mutations has not been studied and compared between defined HBV genotypes. Samples from patients followed during seroconversion from HBeAg to anti‐HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Among 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to genotype B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotypes 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 while the core promoter sequence showed a specific TGA mutation. In another genotype 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 region. In contrast, all genotype D strains showed wild‐type sequences in both the core promoter and precore codon 28 in pre‐ and post‐seroconversion samples. 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 seroconversion to anti‐HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion. J. Med. Virol. 60:107–112, 2000. © 2000 Wiley‐Liss, Inc.