Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H.
Hepatitis B virus (HBV) is a DNA virus that causes liver disease and replicates by reverse transcription of an RNA template. Previous studies have reported that HBV genomes bearing G-->A hypermutation are present at low frequency in human serum. These mutations are most likely due to the activity of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) cytosine deaminases, cellular proteins known to confer innate immunity against retroviruses by generating lethal hypermutations in viral genomes. This study assessed APOBEC3G, APOBEC3C and APOBEC3H, three members of this protein family present in human liver, for their ability to edit HBV genomes. Transfection of human HepG2 hepatoma cells with a plasmid encoding the APOBEC3C protein resulted in abundant G-->A mutations in the majority of newly formed HBV genomes. By contrast, transfection of APOBEC3G- and APOBEC3H-encoding plasmids only marginally increased hypermutation rates above the level caused by the cytosine deaminases naturally present in HepG2 cells. APOBEC3G- and APOBEC3H-mediated hypermutation, however, was clearly revealed by transfection of chicken LMH hepatoma cells, which lack endogenous cytosine deaminases. These results indicate that APOBEC3G, APOBEC3C and APOBEC3H have the ability to edit HBV DNA and that each protein is likely to contribute to various degrees to the generation of modified genomes in human liver cells.
Köck
Josef
J
Department of Medicine II, University of Freiburg, Freiburg, Germany.
Blum
Hubert E
HE
Department of Medicine II, University of Freiburg, Freiburg, Germany.
D000071480:APOBEC-3G Deaminase; D000619:Aminohydrolases; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase; D004279:DNA, Viral / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation
D004279:DNA, Viral; C529313:APOBEC3H protein, human; D000619:Aminohydrolases; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C495795:APOBEC3C protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase