DNA Deamination Mediates Innate Immunity to Retroviral Infection

Cell. 2003 Jun 13;113(6):803-9. doi: 10.1016/s0092-8674(03)00423-9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • Animals
  • Base Sequence / genetics
  • Cell Line
  • Cytidine Deaminase
  • DNA Replication / genetics
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism*
  • Deamination
  • Eukaryotic Cells / metabolism*
  • Gene Products, vif / deficiency
  • Gene Products, vif / genetics
  • HIV / genetics
  • HIV / metabolism*
  • HIV / pathogenicity
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Immunity, Innate / genetics*
  • Leukemia Virus, Murine / genetics
  • Leukemia Virus, Murine / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Nucleoside Deaminases
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Repressor Proteins
  • vif Gene Products, Human Immunodeficiency Virus

Substances

  • DNA, Complementary
  • Gene Products, vif
  • Proteins
  • RNA, Viral
  • Repressor Proteins
  • vif Gene Products, Human Immunodeficiency Virus
  • Nucleoside Deaminases
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase