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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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APOBEC-3G Deaminase
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Animals
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Base Sequence / genetics
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Cell Line
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Cytidine Deaminase
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DNA Replication / genetics
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DNA, Complementary / genetics
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DNA, Complementary / metabolism*
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Deamination
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Eukaryotic Cells / metabolism*
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Gene Products, vif / deficiency
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Gene Products, vif / genetics
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HIV / genetics
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HIV / metabolism*
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HIV / pathogenicity
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HIV Infections / genetics
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HIV Infections / immunology*
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HIV Infections / metabolism
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Humans
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Immunity, Innate / genetics*
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Leukemia Virus, Murine / genetics
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Leukemia Virus, Murine / metabolism
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Nucleoside Deaminases
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Proteins / genetics
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Proteins / metabolism*
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RNA, Viral / biosynthesis
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RNA, Viral / genetics
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Repressor Proteins
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vif Gene Products, Human Immunodeficiency Virus
Substances
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DNA, Complementary
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Gene Products, vif
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Proteins
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RNA, Viral
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Repressor Proteins
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vif Gene Products, Human Immunodeficiency Virus
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Nucleoside Deaminases
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APOBEC-3G Deaminase
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APOBEC3G protein, human
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Cytidine Deaminase