Species-specific Exclusion of APOBEC3G From HIV-1 Virions by Vif

Cell. 2003 Jul 11;114(1):21-31. doi: 10.1016/s0092-8674(03)00515-4.

Abstract

The HIV-1 accessory protein Vif (virion infectivity factor) is required for the production of infectious virions by CD4(+) lymphocytes. Vif facilitates particle infectivity by blocking the inhibitory activity of APOBEC3G (CEM15), a virion-encapsidated cellular protein that deaminates minus-strand reverse transcript cytosines to uracils. We report that HIV-1 Vif forms a complex with human APOBEC3G that prevents its virion encapsidation. HIV-1 Vif did not efficiently form a complex with mouse APOBEC3G. Vif dramatically reduced the amount of human APOBEC3G encapsidated in HIV-1 virions but did not prevent encapsidation of mouse or AGM APOBEC3G. As a result, these enzymes are potent inhibitors of wild-type HIV-1 replication. The species-specificity of this interaction may play a role in restricting HIV-1 infection to humans. Together these findings suggest that therapeutic intervention that either induced APOBEC3G or blocked its interaction with Vif could be clinically beneficial.

Publication types

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

MeSH terms

  • APOBEC-3G Deaminase
  • Animals
  • Antiviral Agents / pharmacology
  • Capsid / metabolism
  • Capsid / virology
  • Cell Line
  • Cytidine Deaminase
  • DNA, Complementary / genetics
  • Gene Expression Regulation, Viral / genetics
  • Gene Products, vif / metabolism*
  • HIV Infections / drug therapy
  • HIV Infections / enzymology*
  • HIV Infections / virology*
  • HIV-1 / enzymology*
  • HIV-1 / pathogenicity
  • Humans
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Nucleoside Deaminases
  • Protein Binding / genetics
  • Proteins / metabolism*
  • Repressor Proteins
  • Species Specificity
  • Transcription, Genetic / genetics
  • Virion / enzymology*
  • Virus Replication / physiology*
  • vif Gene Products, Human Immunodeficiency Virus

Substances

  • Antiviral Agents
  • DNA, Complementary
  • Gene Products, vif
  • Macromolecular Substances
  • Proteins
  • Repressor Proteins
  • vif Gene Products, Human Immunodeficiency Virus
  • Nucleoside Deaminases
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase

Associated data

  • GENBANK/AY331714
  • GENBANK/AY331715
  • GENBANK/AY331716