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Journal of Virology, August 2000, p. 7039-7047, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Interaction of Vpr with Uracil DNA Glycosylase Modulates the Human Immunodeficiency Virus Type 1 In Vivo Mutation Rate

Louis M. Mansky,1,* Sandra Preveral,2 Luc Selig,2,dagger Richard Benarous,2 and Serge Benichou2

Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210,1 and INSERM U529, ICGM, Université Paris V, Paris, France2

Received 8 March 2000/Accepted 1 May 2000

The Vpr protein of human immunodeficiency virus type 1 (HIV-1) influences the in vivo mutation rate of the virus. Since Vpr interacts with a cellular protein implicated in the DNA repair process, uracil DNA glycosylase (UNG), we have explored the contribution of this interaction to the mutation rate of HIV-1. Single-amino-acid variants of Vpr were characterized for their differential UNG-binding properties and used to trans complement vpr null mutant HIV-1. A striking correlation was established between the abilities of Vpr to interact with UNG and to influence the HIV-1 mutation rate. We demonstrate that Vpr incorporation into virus particles is required to influence the in vivo mutation rate and to mediate virion packaging of the nuclear form of UNG. The recruitment of UNG into virions indicates a mechanism for how Vpr can influence reverse transcription accuracy. Our data suggest that distinct mechanisms evolved in primate and nonprimate lentiviruses to reconcile uracil misincorporation into lentiviral DNA.

* Corresponding author. Mailing address: Department of Molecular Virology, Immunology, and Medical Genetics, 2078 Graves Hall, 333 West 10th Ave., Columbus, OH 43210. Phone: (614) 292-5525. Fax: (614) 292-9805. E-mail: mansky.3{at}osu.edu.

dagger Present address: Hybrigenics, Inc., Paris, France.

Journal of Virology, August 2000, p. 7039-7047, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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