HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation

Mariana Marin, Kristine M. Rose, Susan L. Kozak, David Kabat

Research output: Contribution to journalArticle

643 Citations (Scopus)

Abstract

The viral infectivity factor (Vif) encoded by HIV-1 neutralizes a potent antiviral pathway that occurs in human T lymphocytes and several leukemic T-cell lines termed nonpermissive, but not in other cells termed permissive. In the absence of Vif, this antiviral pathway efficiently inactivates HIV-1. It was recently reported that APOBEC3G (also known as CEM-15), a cytidine deaminase nucleic acid-editing enzyme, confers this antiviral phenotype on permissive cells. Here we describe evidence that Vif binds APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Studies of Vif mutants imply that it contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y/F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. These results provide promising approaches for drug discovery.

Original languageEnglish (US)
Pages (from-to)1398-1403
Number of pages6
JournalNature Medicine
Volume9
Issue number11
DOIs
StatePublished - Nov 2003

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Antiviral Agents
HIV-1
T-cells
Degradation
Enzymes
Cytidine Deaminase
T-Lymphocytes
Proteins
Proteasome Endopeptidase Complex
Drug Discovery
Virion
Nucleic Acids
Phenotype
Cell Line

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. / Marin, Mariana; Rose, Kristine M.; Kozak, Susan L.; Kabat, David.

In: Nature Medicine, Vol. 9, No. 11, 11.2003, p. 1398-1403.

Research output: Contribution to journalArticle

Marin, M, Rose, KM, Kozak, SL & Kabat, D 2003, 'HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation', Nature Medicine, vol. 9, no. 11, pp. 1398-1403. https://doi.org/10.1038/nm946
Marin, Mariana ; Rose, Kristine M. ; Kozak, Susan L. ; Kabat, David. / HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. In: Nature Medicine. 2003 ; Vol. 9, No. 11. pp. 1398-1403.
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