APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses.
Endogenous retroviruses are multicopy retroelements accounting for nearly 10% of murine or human genomes. These retroelements spread into our ancestral genome millions of years ago and have acted as a driving force for genome evolution. Endogenous retroviruses may also be deleterious for their host, and have been implicated in cancers and autoimmune diseases. 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. 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. 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. 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.
Esnault
Cécile
C
Unité des Rétrovirus Endogènes et Eléments Retroïdes des Eucaryotes Supérieurs, UMR8122 CNRS, Institut Gustave Roussy, Villejuif 94805, France.
Heidmann
Odile
O
Delebecque
Frédéric
F
Dewannieux
Marie
M
Ribet
David
D
Hance
Allan J
AJ
Heidmann
Thierry
T
Schwartz
Olivier
O
D000071480:APOBEC-3G Deaminase; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D020077:Endogenous Retroviruses / Q000235:genetics*; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics; D009700:Nucleoside Deaminases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D018626:Retroelements / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics
D011506:Proteins; D012097:Repressor Proteins; D018626:Retroelements; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; C496166:APOBEC3G protein, mouse; D003564:Cytidine Deaminase