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Journal of Virology, July 2008, p. 6566-6575, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.01357-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Interactions of Murine APOBEC3 and Human APOBEC3G with Murine Leukemia Viruses{triangledown}

Samuel J. Rulli Jr.,1,{dagger} Jane Mirro,1 Shawn A. Hill,1 Patricia Lloyd,2 Robert J. Gorelick,3 John M. Coffin,4 David Derse,1 and Alan Rein1*

HIV Drug Resistance Program, National Cancer Institute—Frederick,1 Basic Research Laboratory,2 AIDS Vaccine Program, SAIC Frederick, Inc., Frederick, Maryland 21702-1201,3 Department of Microbiology, Tufts University, Boston, Massachusetts 021114

Received 21 June 2007/ Accepted 3 April 2008

APOBEC3 proteins are cytidine deaminases which help defend cells against retroviral infections. One antiviral mechanism involves deaminating dC residues in minus-strand DNA during reverse transcription, resulting in G-to-A mutations in the coding strand. We investigated the effects of mouse APOBEC3 (mA3) and human APOBEC3G (hA3G) upon Moloney murine leukemia virus (MLV). We find that mA3 inactivates MLV but is significantly less effective against MLV than is hA3G. In contrast, mA3 is as potent against human immunodeficiency virus type 1 (HIV-1, lacking the protective Vif protein) as is hA3G. The two APOBEC3 proteins are packaged to similar extents in MLV particles. Dose-response profiles imply that a single APOBEC3 molecule (or oligomer) is sufficient to inactivate an MLV particle. The inactivation of MLV by mA3 and hA3G is accompanied by relatively small reductions in the amount of viral DNA in infected cells. Although hA3G induces significant levels of G-to-A mutations in both MLV and HIV DNAs, and mA3 induces these mutations in HIV DNA, no such mutations were detected in DNA synthesized by MLV inactivated by mA3. Thus, MLV has apparently evolved to partially resist the antiviral effects of mA3 and to totally resist the ability of mA3 to induce G-to-A mutation in viral DNA. Unlike the resistance of HIV-1 and human T-cell leukemia virus type 1 to hA3G, the resistance of MLV to mA3 is not mediated by the exclusion of APOBEC from the virus particle. The nature of its resistance and the mechanism of inactivation of MLV by mA3 are completely unknown.

* Corresponding author. Mailing address: National Cancer Institute—Frederick, P.O. Box B, Frederick, MD 12702-1201. Phone: (301) 846-1361. Fax: (301) 846-6013. E-mail: rein{at}ncifcrf.gov

{triangledown} Published ahead of print on 30 April 2008.

{dagger} Present address: SuperArray Biosciences, Frederick, MD 21704.

Journal of Virology, July 2008, p. 6566-6575, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.01357-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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