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APOBEC3 inhibits mouse mammary tumour virus replication in vivo

Abstract

Genomes of all mammals encode apobec3 genes, which are thought to have a function in intrinsic cellular immunity to several viruses including human immunodeficiency virus type 1 (HIV-1)1. APOBEC3 (A3) proteins are packaged into virions and inhibit retroviral replication in newly infected cells, at least in part by deaminating cytidines on the negative strand DNA intermediates2. However, the role of A3 in innate resistance to mouse retroviruses is not understood. Here we show that A3 functions during retroviral infection in vivo and provides partial protection to mice against infection with mouse mammary tumour virus (MMTV). Both mouse A3 and human A3G proteins interacted with the MMTV nucleocapsid in an RNA-dependent fashion and were packaged into virions. In addition, mouse A3-containing and human A3G-containing virions showed a marked decrease in titre. Last, A3-/- mice were more susceptible to MMTV infection, because virus spread was more rapid and extensive than in their wild-type littermates.

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Figure 1: mA3 and hA3G are incorporated into MMTV virions and bind NC.
Figure 2: mA3 and hA3G inhibit MMTV replication in vitro.
Figure 3: mA3 inhibits MMTV infection in vivo.
Figure 4: mA3 inhibits virus infection and spread in vivo.

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Acknowledgements

The CGRES6 cells and pGR102ES plasmid were a gift from F. Roualt and W. Günzburg. This study was supported by grants from the National Institutes of Health to S.R.R. and M.B.P. C.O. was supported by a training grant from the National Cancer Institute of the National Institutes of Health and N.L. was funded in part by the Slovenian Research Agency.

Author Contributions C.M.O, N.L., B.M.P. and S.R.R. designed the research. C.M.O. and N.L. performed the research. C.M.O, N.L., B.M.P. and S.R.R. wrote the paper.

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Correspondence to Susan R. Ross.

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Okeoma, C., Lovsin, N., Peterlin, B. et al. APOBEC3 inhibits mouse mammary tumour virus replication in vivo. Nature 445, 927–930 (2007). https://doi.org/10.1038/nature05540

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