The Cytidine Deaminase CEM15 Induces Hypermutation in Newly Synthesized HIV-1 DNA

Nature. 2003 Jul 3;424(6944):94-8. doi: 10.1038/nature01707. Epub 2003 May 28.

Abstract

High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture. The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G), an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • APOBEC-3G Deaminase
  • Cell Line
  • Cytidine Deaminase
  • DNA, Viral / biosynthesis*
  • DNA, Viral / genetics*
  • Gene Products, vif / deficiency
  • Gene Products, vif / genetics
  • Gene Products, vif / metabolism
  • HIV-1 / genetics*
  • HIV-1 / growth & development
  • HIV-1 / physiology
  • Humans
  • Mutagenesis / genetics*
  • Nucleoside Deaminases
  • Point Mutation / genetics
  • Proteins / genetics
  • Proteins / metabolism*
  • Repressor Proteins
  • Serial Passage
  • Transcription, Genetic / genetics
  • Virus Replication
  • vif Gene Products, Human Immunodeficiency Virus

Substances

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