DNA determination mediates innate immunity to retroviral infection
DNA determination mediates innate immunity to retroviral infection
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DOI：
10.1016/s0092-8674(03)00423-9
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发表时间：
2003-06-13
期刊：
影响因子：
64.5
通讯作者：
Malim, MH
中科院分区：
文献类型：
--
作者：
Harris, RS;Bishop, KN;Malim, MH
CEM15/APOBEC3G是一种细胞蛋白，是对缺乏病毒感染因子（Vif）的人类免疫缺陷病毒（HIV）感染产生抗性所必需的。在此，我们利用基于鼠白血病病毒（MLV）的系统，提供证据表明CEM15/APOBEC3G是一种DNA脱氨酶，它在病毒产生过程中被整合到病毒粒子中，随后在逆转录病毒负（第一）链cDNA内引发大量的脱氧胞苷脱氨转化为脱氧尿苷，从而可能引发病毒的破坏。此外，HIV的Vif能够保护MLV免受这种依赖于CEM15/APOBEC3G的限制。这些发现意味着靶向DNA脱氨是针对逆转录病毒的先天免疫的一种主要策略，并且可能也有助于许多病毒（包括HIV）中所观察到的序列变异。
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).