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Journal of Virology, December 2007, p. 13346-13353, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01361-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Enzymatically Active APOBEC3G Is Required for Efficient Inhibition of Human Immunodeficiency Virus Type 1{triangledown}

Eri Miyagi,{dagger} Sandrine Opi,{dagger} Hiroaki Takeuchi, Mohammad Khan, Ritu Goila-Gaur, Sandra Kao, and Klaus Strebel*

Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-0460

Received 22 June 2007/ Accepted 30 September 2007

APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. Initial studies of the function of APO3G demonstrated extensive mutation of the viral genome, suggesting a model in which APO3G's antiviral activity is due to hypermutation of the viral genome. Recent studies, however, found that deaminase-defective APO3G mutants transiently expressed in virus-producing cells exhibited significant antiviral activity, suggesting that the antiviral activity of APO3G could be dissociated from its deaminase activity. To directly compare the antiviral activities of wild-type (wt) and deaminase-defective APO3G, we used two approaches: (i) we titrated wt and deaminase-defective APO3G in transient-transfection studies to achieve similar levels of virus-associated APO3G and (ii) we constructed stable cell lines and selected clones expressing comparable amounts of wt and deaminase-defective APO3G. Viruses produced under these conditions were tested for viral infectivity. The results from the two approaches were consistent and suggested that the antiviral activity of deaminase-defective APO3G was significantly lower than that of wt APO3G. We conclude that efficient inhibition of vif-defective human immunodeficiency virus type 1 requires catalytically active APO3G.

* Corresponding author. Mailing address: Viral Biochemistry Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bldg. 4, Room 310, 4 Center Drive, MSC 0460, Bethesda, MD 20892-0460. Phone: (301) 496-3132. Fax: (301) 402-0226. E-mail: kstrebel{at}nih.gov

{triangledown} Published ahead of print on 10 October 2007.

{dagger} These authors equally contributed to this work.

Journal of Virology, December 2007, p. 13346-13353, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01361-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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