DNA deamination mediates innate immunity to retroviral infection

Reuben S. Harris, Kate N. Bishop, Ann M. Sheehy, Heather M. Craig, Svend K. Petersen-Mahrt, Ian N. Watt, Michael S. Neuberger, Michael H. Malim

Research output: Contribution to journalArticlepeer-review

1170 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)803-809
Number of pages7
JournalCell
Volume113
Issue number6
DOIs
StatePublished - Jun 13 2003
Externally publishedYes

Bibliographical note

Funding Information:
We thank R. Grenfell and W. Turnbull for assistance with flow cytometry; F. Randow and J. Stoye for reagents; and A. Lenton for help with figures. We are also grateful for interactions with R.C.L. Beale, J. Butler, J. Di Noia, D. MacDuff, and F. Randow. This work was in part supported by grants from the Medical Research Council (to M.H.M.), the Leukaemia Research Fund (to R.S.H., I.N.W and M.S.N.), the Arthritis Research Campaign (to S.K.P.-M. and M.S.N.) and the Royal Society (to A.M.S.). M.H.M. is an Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation.

Fingerprint

Dive into the research topics of 'DNA deamination mediates innate immunity to retroviral infection'. Together they form a unique fingerprint.

Cite this