APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses

Abstract

Endogenous retroviruses are multicopy retroelements accounting for nearly 10% of murine or human genomes^1,2. These retroelements spread into our ancestral genome millions of years ago and have acted as a driving force for genome evolution^2,3,4. 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 mobile^6,7. 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 methylation^4,8. 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 replication^9,10,11,12. 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.