Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G-->A hypermutation.
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 > or = 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.
Günther
S
S
Heinrich-Pette-Institut fur Experimentelle Virologie und Immunologie, Hamburg, Germany.
Sommer
G
G
Plikat
U
U
Iwanska
A
A
Wain-Hobson
S
S
Will
H
H
Meyerhans
A
A
D000225:Adenine; D001483:Base Sequence; D002353:Carrier State / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral / Q000737:chemistry; D015226:Dinucleoside Phosphates / Q000032:analysis / Q000737:chemistry; D016368:Frameshift Mutation; D016679:Genome, Viral; D006147:Guanine; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017384:Sequence Deletion
D017931:DNA Primers; D004279:DNA, Viral; D015226:Dinucleoside Phosphates; D006147:Guanine; D000225:Adenine