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Journal of Virology, November 2009, p. 11550-11559, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01430-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The AKV Murine Leukemia Virus Is Restricted and Hypermutated by Mouse APOBEC3{triangledown}

Marc-André Langlois,* Kristin Kemmerich, Cristina Rada, and Michael S. Neuberger

Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, United Kingdom CB2 0QH

Received 10 July 2009/ Accepted 24 August 2009

APOBEC3 proteins are potent restriction factors against retroviral infection in primates. This restriction is accompanied by hypermutations in the retroviral genome that are attributable to the cytidine deaminase activity of the APOBEC3 proteins. Studies of nucleotide sequence diversity among endogenous gammaretroviruses suggest that the evolution of endogenous retroelements could have been shaped by the mutagenic cytidine deaminase activity of APOBEC3. In mice, however, APOBEC3 appears to restrict exogenous murine retroviruses in the absence of detectable levels of deamination. AKV is an endogenous retrovirus that is involved in causing a high incidence of thymic lymphoma in AKR mice. A comparative analysis of several mouse strains revealed a relatively low level of APOBEC3 expression in AKR mice. Here we show that endogenous mouse APOBEC3 restricts AKV infection and that this restriction likely reflects polymorphisms affecting APOBEC3 abundance rather than differences in the APOBEC3 isoforms expressed. We also observe that restriction of AKV by APOBEC3 is accompanied by G->A hypermutations in the viral genome. Our findings demonstrate that APOBEC3 acts as a restriction factor in rodents affecting the strain tropism of AKV, and they provide good support for the proposal that APOBEC3-mediated hypermutation contributed to the evolution of endogenous rodent retroviral genomes.

* Corresponding author. Present address: Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa. 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. Phone: (613) 562-5800, ext. 7110. Fax: (613) 562-5442. E-mail: langlois{at}uottawa.ca

{triangledown} Published ahead of print on 2 September 2009.

Journal of Virology, November 2009, p. 11550-11559, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01430-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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