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Functional Central Polypurine Tract Provides Downstream Protection of the Human Immunodeficiency Virus Type 1 Genome from Editing by APOBEC3G and APOBEC3B

Sebastien Wurtzer, Armelle Goubard, Fabrizio Mammano, Sentob Saragosti, Denise Lecossier, Allan J. Hance, and François Clavel^*

Unité de Recherche Antivirale, INSERM U552, and Faculté de Médecine, Université Paris 7 Denis Diderot, Paris F-75018, France

Received 22 August 2005/ Accepted 10 January 2006

Lentiviruses utilize two polypurine tracts for initiation of plus-strand viral DNA synthesis. We have examined to what extent human immunodeficiency virus type 1 plus-strand initiation at the central polypurine tract (cPPT) could protect the viral genome from DNA editing by APOBEC3G and APOBEC3B. The presence of a functional cPPT, but not of a mutated cPPT, extensively reduced editing by both APOBEC3G and APOBEC3B of sequences downstream, but not upstream, of the cPPT, with significant protection observed as far as 400 bp downstream. Thus, in addition to other potential functions, the cPPT could help protect lentiviruses from editing by cytidine deaminases of the APOBEC family.

S.W. and A.G. contributed equally to this study.

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