Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo.
Because the replication of hepatitis B virus (HBV) proceeds via an obligatory reverse transcription step in the viral capsid, cDNA is potentially vulnerable to editing by cytidine deaminases of the APOBEC3 family. To date only two edited HBV genomes, referred to as G --> A hypermutants, have been described in vivo. Recent work suggested that HBV replication was indeed restricted by APOBEC3G but by a mechanism other than editing. The issue of restriction has been explored by using a sensitive PCR method allowing differential amplification of AT-rich DNA. G --> A hypermutated HBV genomes were recovered from transfection experiments involving APOBEC3B, -3C, -3F, and -3G indicating that all four enzymes were able to extensively deaminate cytidine residues in minus-strand DNA. Unexpectedly, three of the four enzymes (APOBEC3B, -3F, and -3G) deaminated HBV plus-strand DNA as well. From the serum of two of four patients with high viremia, G --> A hypermutated genomes were recovered at a frequency of approximately 10(-4), indicating that they are, albeit relatively rare, part of the natural cycle of HBV infection. These findings suggest that human APOBEC3 enzymes can impact HBV replication via cytidine deamination.
Suspène
Rodolphe
R
Molecular Retrovirology (Centre National de la Recherche Scientifique Unité de Recherche Associée 1930) Paris Cedex 15, France.
Guétard
Denise
D
Henry
Michel
M
Sommer
Peter
P
Wain-Hobson
Simon
S
Vartanian
Jean-Pierre
JP
D000071480:APOBEC-3G Deaminase; D001483:Base Sequence; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D009700:Nucleoside Deaminases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins
D004279:DNA, Viral; D015778:Minor Histocompatibility Antigens; D011506:Proteins; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C495794:APOBEC3B protein, human; C495795:APOBEC3C protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase