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Journal of Virology, December 2007, p. 13694-13699, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01646-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Alpharetrovirus Replication by a Range of Human APOBEC3 Proteins{triangledown}

Heather L. Wiegand and Bryan R. Cullen*

Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710

Received 27 July 2007/ Accepted 19 September 2007

The mammalian APOBEC3 family of cytidine deaminases includes members that can act as potent inhibitors of retroviral infectivity and retrotransposon mobility. Here, we have examined whether the alpharetrovirus Rous sarcoma virus (RSV) is susceptible to inhibition by a range of human APOBEC3 proteins. We report that RSV is highly susceptible to inhibition by human APOBEC3G, APOBEC3F, and APOBEC3B and moderately susceptible to inhibition by human APOBEC3C and APOBEC3A. For all five proteins, inhibition of RSV infectivity was associated with selective virion incorporation and with C-to-T editing of the proviral DNA minus strand. In the case of APOBEC3G, editing appeared to be critical for effective inhibition. These data represent the first report of inhibition of retroviral infectivity and induction of proviral DNA editing by human APOBEC3A and reveal that alpharetroviruses, which do not normally encounter APOBEC3 proteins in their avian hosts, are susceptible to inhibition by all human APOBEC3 proteins tested. These data further suggest that the resistance of mammalian retroviruses to inhibition by the APOBEC3 proteins expressed in their normal host species is likely to have evolved subsequent to the appearance of this family of mammalian antiretroviral proteins some 35 million years ago; i.e., the base state of a naïve retrovirus is susceptibility to inhibition.

* Corresponding author. Mailing address: Duke University Medical Center, Box 3025, Durham, NC 27710. Phone: (919) 684-3369. Fax: (919) 681-8979. E-mail: culle002{at}mc.duke.edu

{triangledown} Published ahead of print on 3 October 2007.

Journal of Virology, December 2007, p. 13694-13699, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01646-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bogerd, H. P., Cullen, B. R. (2008). Single-stranded RNA facilitates nucleocapsid: APOBEC3G complex formation. RNA 14: 1228-1236 [Abstract] [Full Text]  
  • Kock, J., Blum, H. E. (2008). Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H. J. Gen. Virol. 89: 1184-1191 [Abstract] [Full Text]  
  • Langlois, M.-A., Neuberger, M. S. (2008). Human APOBEC3G Can Restrict Retroviral Infection in Avian Cells and Acts Independently of both UNG and SMUG1. J. Virol. 82: 4660-4664 [Abstract] [Full Text]  


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