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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
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The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation

John P Donahue1, Michael L Vetter, Nizar A Mukhtar

  • 1Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, A-2200, Medical Center North, Nashville, TN 37232, USA. john.donahue@vanderbilt.edu

Virology
|May 24, 2008
PubMed

Insights

The HIV-1 Vif protein’s PPLP motif is crucial for binding APOBEC3G, preventing viral infectivity loss. Mutations here impair Vif-A3G interaction, leading to A3G in virions and reduced infectivity.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • The HIV-1 virion infectivity factor (Vif) counteracts host restriction factors like APOBEC3G (A3G).
  • Vif targets A3G for proteasomal degradation via a Cullin5-ElonginBC E3 ubiquitin ligase complex.
  • The PPLP motif in Vif is known to be essential for its function in T-cells.

Purpose of the Study:

  • To investigate the role of the Vif PPLP motif in the interaction with A3G and the E3 ligase complex.
  • To determine how mutations in the PPLP motif affect Vif function and viral infectivity.

Main Methods:

  • Site-directed mutagenesis of the Vif PPLP motif.
  • Co-immunoprecipitation assays to assess protein-protein interactions (Vif-A3G, Vif-ElonginC, Vif-Cullin5).
  • Analysis of A3G incorporation into virions and assessment of viral infectivity.

Main Results:

  • Mutation of the Vif PPLP motif significantly reduced Vif binding to A3G.
  • The Vif PPLP mutation did not affect the interaction between Vif and ElonginC or Cullin5.
  • Mutant Vif failed to prevent A3G incorporation into assembling virions, leading to a loss of viral infectivity.

Conclusions:

  • The Vif PPLP motif is critical for mediating the interaction between Vif and A3G.
  • Disruption of the Vif-A3G interaction by PPLP mutation leads to A3G packaging into virions.
  • This packaging of A3G results in non-infectious virions, highlighting the importance of Vif in HIV-1 replication.

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