Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa

• Published in: Journal of general virology 2004-05, Vol.85 (5), p.1211-1220
• Main Authors: Kimbi, Gerald C, Kramvis, Anna, Kew, Michael C
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carrier State; Fundamental and applied biological sciences. Psychology; Genes, Regulator - genetics; Genome, Viral; Hepatitis B - etiology; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - classification; Hepatitis B virus - genetics; Human viral diseases; Humans; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation; Open Reading Frames; Phylogeny; South Africa; Viral diseases; Viral hepatitis; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.19749-0

MRC/CANSA/University Molecular Hepatology Research Unit and Department of Medicine, University of the Witwatersrand, Parktown 2193, Johannesburg, South Africa Correspondence Anna Kramvis kramvisa{at}medicine.wits.ac.za Phylogenetic analysis of hepatitis B virus (HBV) has led to its classification into eight genotypes, A to H. The dominant genotype in South Africa is genotype A, which consists of two subgenotypes, A1 and A2. Subgenotype A1 (previously subgroup A') predominates over subgenotype A2 (previously subgroup A minus A'). The complete genome of HBV isolated from 18 asymptomatic carriers of the virus and five acute hepatitis B patients was amplified; the resulting amplicons were cloned and sequenced. All acute hepatitis isolates belonged to subgenotype A1 and had no distinguishing mutations relative to the isolates from asymptomatic carriers, which had a distribution of ten subgenotype A1, two subgenotype A2 and six genotype D. The presence of the previously described amino acid residues that distinguish subgenotype A1 (subgroup A') from the remainder of genotype A in the S and polymerase genes was confirmed. Moreover, the large number of subgenotype A1 isolates sequenced allowed identification in the other open reading frames of additional nucleotide and amino acid changes that are characteristic of subgenotype A1. In particular, nucleotide mutations at positions 1809–1812 that alter the Kozak sequence of the precore/core open reading frame, and A 1888 in the precore region, were found exclusively in subgenotype A1 isolates. Unique sequence alterations of the transcriptional regulatory elements were also found in subgenotype A1 isolates. The mean nucleotide divergence of subgenotype A1 was greater than that of subgenotype A2, suggesting that this subgenotype has been endemic for a longer time in the South African black population than had subgenotype A2. The accession numbers of hepatitis B virus isolates sequenced in this study have been deposited in GenBank/EMBL/DDBJ as AY233274 – AY233296 .