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J. Biol. Chem., Vol. 282, Issue 44, 32065-32074, November 2, 2007

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APOBEC3G Inhibits DNA Strand Transfer during HIV-1 Reverse Transcription^*

Xiao-Yu Li, Fei Guo, Li Zhang, Lawrence Kleiman^¶1, and Shan Cen^||2

From the Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Departments of Medicine and of ^¶Microbiology & Immunology, McGill University, Montreal, Quebec H3T 1E2, Canada and the ^||Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China

Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability of the virus to produce new viral DNA upon infection. In this report, we demonstrate that the reduction of late viral DNA synthesis is due to the inhibition by hA3G of the strand transfer steps that occur during reverse transcription. Analysis of viral cDNA intermediates in vivo reveals that hA3G causes an inhibition of the minus and plus strand transfers, without having a significant impact on DNA elongation. Using an in vitro system to measure minus strand transfer similarly shows a dose-dependent reduction of strand transfer by hA3G. This inhibition of strand transfer occurs independently the editing activity of hA3G and is correlated with its ability to prevent RNaseH degradation of the template RNA.

Received for publication, April 24, 2007 , and in revised form, August 29, 2007.

^* This work was supported by the Canadian Foundation for AIDS Research (Grant 017018 to S. C. and L. K.), by the Canadian Institutes for Health Research (CIHR) (Grant 115315 to S. C.), and by the CIHR (Grant 15571 to L. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence may be addressed: Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Rd., Montreal, Quebec H3T 1E2, Canada. Tel.: 514-340-8260 (ext. 5285); Fax: 514-340-7502; E-mail: lawrence.kleiman{at}mcgill.ca. ² To whom correspondence may be addressed: Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Rd., Montreal, Quebec H3T 1E2, Canada. Tel: 514-340-8260 (ext. 5297); Fax: 514-340-7502; E-mail: shan.cen{at}mcgill.ca.

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