Naturally Occurring Hepatitis B Virus Genomes Bearing the Hallmarks of Retroviral G → A Hypermutation

• Published in: Virology (New York, N.Y.) N.Y.), 1997-08, Vol.235 (1), p.104-108
• Main Authors: Günther, Stephan, Sommer, Gunhild, Plikat, Uwe, Iwanska, Alicja, Wain-Hobson, Simon, Will, Hans, Meyerhans, Andreas
• Format: Article
• Language: English
• Subjects: Adenine; Base Sequence; Carrier State - virology; Dinucleoside Phosphates - analysis; Dinucleoside Phosphates - chemistry; DNA Primers; DNA, Viral - chemistry; Frameshift Mutation; Genome, Viral; Guanine; Hepatitis B - virology; Hepatitis B virus - genetics; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Point Mutation; Polymerase Chain Reaction; Sequence Alignment; Sequence Deletion
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1997.8676

Two hypermutated genomes of hepatitis B virus (HBV) were cloned from sera of chronic virus carriers. Twelve percent and 26% of guanosine residues were replaced by adenosine, with the transitions being erratically distributed along the genome. G → A substitutions showed a strong dinucleotide preference, decreasing in the order GpA > GpG ⪢ GpC ≥ GpT. Such traits are typical of retroviral G → A hypermutation which results from cDNA synthesis coinciding with fluctuations in the intracellular [dTTP]/[dCTP] ratio. The observations offer an explanation for the high prevalence of HBV variants bearing a tryptophan 28 → stop codon in the pre-core region of carriers with chronic active or fulminant hepatitis. The HBV hypermutants indicate that a small proportion of hepatocytes have distorted dNTP pools, which might have implications for the fidelity of hepatocyte DNA replication or repair.