HIV-1 Vif Blocks the Antiviral Activity of APOBEC3G by Impairing Both Its Translation and Intracellular Stability

Mol Cell. 2003 Sep;12(3):591-601. doi: 10.1016/s1097-2765(03)00353-8.

Abstract

The human immunodeficiency virus type 1 (HIV-1) relies on Vif (viral infectivity factor) to overcome the potent antiviral function of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, also known as CEM15). Using an APOBEC3G-specific antiserum, we now show that Vif prevents virion incorporation of endogenous APOBEC3G by effectively depleting the intracellular levels of this enzyme in HIV-1-infected T cells. Vif achieves this depletion by both impairing the translation of APOBEC3G mRNA and accelerating the posttranslational degradation of the APOBEC3G protein by the 26S proteasome. Vif physically interacts with APOBEC3G, and expression of Vif alone in the absence of other HIV-1 proteins is sufficient to cause depletion of APOBEC3G. These findings highlight how the bimodal translational and posttranslational inhibitory effects of Vif on APOBEC3G combine to markedly suppress the expression of this potent antiviral enzyme in virally infected cells, thereby effectively curtailing the incorporation of APOBEC3G into newly formed HIV-1 virions.

Publication types

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

MeSH terms

  • APOBEC-3G Deaminase
  • Cytidine Deaminase
  • Cytoplasm / metabolism
  • Down-Regulation / physiology
  • Enzyme Inhibitors / pharmacology
  • Gene Products, vif / genetics
  • Gene Products, vif / metabolism*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HIV-1 / pathogenicity
  • Humans
  • Jurkat Cells
  • Nucleoside Deaminases
  • Peptide Hydrolases / metabolism
  • Protein Binding / physiology
  • Protein Biosynthesis* / genetics
  • Protein Processing, Post-Translational
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Repressor Proteins
  • Virion / genetics
  • Virion / metabolism
  • Virus Replication / physiology*
  • vif Gene Products, Human Immunodeficiency Virus

Substances

  • Enzyme Inhibitors
  • Gene Products, vif
  • Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • vif Gene Products, Human Immunodeficiency Virus
  • Psmd7 protein, mouse
  • Peptide Hydrolases
  • Nucleoside Deaminases
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase