APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses

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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.