Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G->A hypermutation

被引:63
作者
Gunther, S
Sommer, G
Plikat, U
Iwanska, A
WainHobson, S
Will, H
Meyerhans, A
机构
[1] UNIV FREIBURG,INST MED MIKROBIOL & HYG,ABT VIROL,D-79104 FREIBURG,GERMANY
[2] HEINRICH PETTE INST EXPT VIROL & IMMUNOL,D-20251 HAMBURG,GERMANY
[3] INST PASTEUR,UNITE RETROVIROL MOL,F-75724 PARIS 15,FRANCE
关键词
D O I
10.1006/viro.1997.8676
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 much greater than GpC greater than or equal to Gpi: 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. (C) 1997 Academic Press.
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页码:104 / 108
页数:5
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