title: Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and the recombinant nature of APOBEC3G.
abstract: Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10(-2) to 10(-5)in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR ( approximately 10(-4) to 10(-5)). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1Deltavif efficiently.
authors.affiliation: Molecular Retrovirology Unit, CNRS URA 3015, Institut Pasteur, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Henry
authors.forename: Denise
authors.initials: D
authors.lastname: Guétard
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
authors.forename: Christophe
authors.initials: C
authors.lastname: Rusniok
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vartanian
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics* / Q000502:physiology; D004279:DNA, Viral; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011784:Quail; D017393:RNA Editing; D011994:Recombinant Proteins / Q000737:chemistry; D014779:Virus Replication / Q000235:genetics
chemical_list: D004279:DNA, Viral; D011994:Recombinant Proteins; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase