DNA deamination mediates innate immunity to retroviral infection.
CEM15/APOBEC3G is a cellular protein required for resistance to infection by virion infectivity factor (Vif)-deficient human immunodeficiency virus (HIV). Here, using a murine leukemia virus (MLV)-based system, we provide evidence that CEM15/APOBEC3G is a DNA deaminase that is incorporated into virions during viral production and subsequently triggers massive deamination of deoxycytidine to deoxyuridine within the retroviral minus (first)-strand cDNA, thus providing a probable trigger for viral destruction. Furthermore, HIV Vif can protect MLV from this CEM15/APOBEC3G-dependent restriction. These findings imply that targeted DNA deamination is a major strategy of innate immunity to retroviruses and likely also contributes to the sequence variation observed in many viruses (including HIV).
Harris
Reuben S
RS
Medical Research Council Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, United Kingdom. rharris@mrc-lmb.cam.ac.uk
Bishop
Kate N
KN
Sheehy
Ann M
AM
Craig
Heather M
HM
Petersen-Mahrt
Svend K
SK
Watt
Ian N
IN
Neuberger
Michael S
MS
Malim
Michael H
MH
D000071480:APOBEC-3G Deaminase; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D003564:Cytidine Deaminase; D004261:DNA Replication / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism*; D003641:Deamination; D005057:Eukaryotic Cells / Q000378:metabolism*; D016346:Gene Products, vif / Q000172:deficiency / Q000235:genetics; D006678:HIV / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009700:Nucleoside Deaminases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus
D018076:DNA, Complementary; D016346:Gene Products, vif; D011506:Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase