A powerful mechanism of vertebrate innate immunity has been discovered in the past year, in which APOBEC proteins inhibit retroviruses by deaminating cytosine residues in nascent retroviral cDNA. To thwart this cellular defence, HIV encodes Vif, a small protein that mediates APOBEC degradation. Therefore, the balance between APOBECs and Vif might be a crucial determinant of the outcome of retroviral infection. Vertebrates have up to 11 different APOBEC proteins, with primates having the most. APOBEC proteins include AID, a probable DNA mutator that is responsible for immunoglobulin-gene diversification, and APOBEC1, an RNA editor with antiretroviral activities. This APOBEC abundance might help to tip the balance in favour of cellular defences.
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We are grateful to our laboratory and neighbouring colleagues for helpful comments, especially E. Hendrickson, D. Livingston, P. Magee and L. Mansky. We also thank T. Floss and the reviewers for helpful comments. R.S.H. is supported by a Burroughs–Wellcome Fund Hitchings Elion Fellowship (United States), the Searle Scholars Program (United States) and a new laboratory start-up award from the University of Minnesota (United States).