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APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses

Nature volume 433, pages 430–433 (2005)Cite this article

Abstract

Endogenous retroviruses are multicopy retroelements accounting for nearly 10% of murine or human genomes1,2. These retroelements spread into our ancestral genome millions of years ago and have acted as a driving force for genome evolution2,3,4. Endogenous retroviruses may also be deleterious for their host, and have been implicated in cancers and autoimmune diseases5. Most retroelements have lost replication competence because of the accumulation of inactivating mutations, but several, including some murine intracisternal A-particle (IAP) and MusD sequences, are still mobile6,7. These elements encode a reverse transcriptase activity and move by retrotransposition, an intracellular copy-and-paste process involving an RNA intermediate. The host has developed mechanisms to silence their expression, mainly cosuppression and gene methylation4,8. Here we identify another level of antiviral control, mediated by APOBEC3G, a member of the cytidine deaminase family that was previously shown to block HIV replication9,10,11,12. We show that APOBEC3G markedly inhibits retrotransposition of IAP and MusD elements, and induces G-to-A hypermutations in their DNA copies. APOBEC3G, by editing viral genetic material, provides an ancestral wide cellular defence against endogenous and exogenous invaders.

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Figure 1: APOBEC3G inhibits the retrotransposition of endogenous retroviruses.
Figure 2: APOBEC3G promotes G-to-A hypermutation of endogenous retroviruses.
Figure 3: Distribution of nucleotide substitutions in MusD, IAP and L1Md retroelements present in the mouse genome.
Figure 4: Influence of neighbouring nucleotides on G-to-A mutations in retroelements present in the mouse genome.

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Acknowledgements

We thank S. Wain-Hobson for useful comments, N. Landau and the NIH AIDS reagents program for the gift of reagents. This work was supported by grants from the Institut Pasteur, the Institut Gustave Roussy, the ANRS, Sidaction, the Ligue Nationale contre le Cancer, the CNRS, INSERM and the European Community. F.D. is a fellow of Sidaction. Some relevant original papers have not been cited owing to space constraints.

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  1. Thierry Heidmann and Olivier Schwartz: These authors contributed equally to this work

Authors and Affiliations

  1. Unité des Rétrovirus Endogènes et Éléments Retroïdes des Eucaryotes Supérieurs, UMR8122 CNRS, Institut Gustave Roussy, Villejuif, 94805, France

    Cécile Esnault, Odile Heidmann, Marie Dewannieux, David Ribet & Thierry Heidmann

  2. Virus and Immunity Group, Department of Virology, Institut Pasteur, CNRS URA1930, 75015, Paris, France

    Cécile Esnault, Frédéric Delebecque & Olivier Schwartz

  3. INSERM U552, Hôpital Bichat-Claude Bernard, 75018, Paris, France

    Allan J. Hance

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Correspondence to Thierry Heidmann or Olivier Schwartz.

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Supplementary information

Supplementary Figure S1

IAP and MusD base mutation spectra induced by APOBEC3G in the cell-based retrotransposition assay. (PPT 89 kb)

Supplementary Figure S2

Distibution of G-to-A hypermutations in MusD sequences found in the mouse genome. (PPT 134 kb)

Supplementary Figure Legends

This file contains legends to Supplementary Figures. (DOC 23 kb)

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Esnault, C., Heidmann, O., Delebecque, F. et al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature 433, 430–433 (2005). https://doi.org/10.1038/nature03238

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