DNA determination mediates innate immunity to retroviral infection

被引:1119
作者
Harris, RS
Bishop, KN
Sheehy, AM
Craig, HM
Petersen-Mahrt, SK
Watt, IN
Neuberger, MS
Malim, MH
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Kings Coll London, Guys Kings & St Thomas Sch Med, Dept Infect Dis, London SE1 9RT, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(03)00423-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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).
引用
收藏
页码:803 / 809
页数:7
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