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Published online 30 April 2004

Nucleic Acids Research, 2004, Vol. 32, No. 8 2421-2429
© 2004 Oxford University Press

APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase

Rodolphe Suspène1, Peter Sommer1, Michel Henry1, Stéphane Ferris2, Denise Guétard1, Sylvie Pochet3, Ann Chester4, Naveenan Navaratnam4, Simon Wain-Hobson*,1 and Jean-Pierre Vartanian1

1 Unité de Rétrovirologie Moléculaire, 2 Service de la Coordination Scientifique, 3 Unité de Chimie Organique, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France and 4 MRC, Clinical Sciences Centre, RNA Editing Group, Faculty of Medicine, Imperial College School of Medicine, Du Cane Road, London W12 ONN, UK

*To whom correspondence should be addressed. Tel: +33 1 45 68 88 21; Fax: +33 1 45 68 88 74; Email: simon{at}pasteur.fr

Received March 5, 2004; Revised and Accepted March 30, 2004

In the absence of the viral vif gene, human immunodeficiency virus (HIV) may be restricted by the APOBEC3G gene on chromosome 22. The role of the HIV Vif protein is to exclude host cell APOBEC3G from the budding virion. As APOBEC3G shows sequence homology to cytidine deaminases, it is presumed that in the absence of Vif, cytidine residues in the cDNA are deaminated yielding uracil. It is not known if additional proteins mediate APOBEC3G function or if deamination occurs in concert with reverse transcription. This report describes an in vitro assay showing that Baculovirus derived APOBEC3G alone extensively deaminates cDNA independently of reverse transcriptase. It reproduces the dinucleotide context typical of G -> A hypermutants derived from a {Delta}vif virus. By using an RNaseH– form of reverse transcriptase, it was shown that the cDNA has to be free of its RNA template to allow deamination. APOBEC3G deamination of dC or dCTP was not detected. In short, APOBEC3G is a single-stranded DNA cytidine deaminase capable of restricting retroviral replication.


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