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HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1

Bärbel Schröfelbauer1, Yoshiyuki Hakata, Nathaniel R Landau

  • 1Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 16, 2007
PubMed

Insights

The HIV-1 Vpr protein binds to DDB1, a DNA repair protein. This interaction causes Vpr-induced apoptosis, DNA repair impairment, and viral replication, explaining Vpr

Area of Science:

  • Molecular Biology
  • Virology
  • Cellular Biology

Background:

  • The HIV-1 Vpr protein mimics DNA damage responses, activating ATR kinase, causing G2 arrest and apoptosis.
  • Vpr induces degradation of uracil-DNA glycosylases UNG2 and SMUG1.
  • The mechanism of Vpr's biological effects and its interacting partners remain unclear.

Purpose of the Study:

  • To identify cellular proteins that bind to the HIV-1 Vpr protein.
  • To elucidate the mechanism by which Vpr mediates its biological effects, including apoptosis and DNA repair inhibition.

Main Methods:

  • Tandem affinity purification coupled with mass spectrometry to identify Vpr-binding proteins.
  • Functional assays to assess the role of Vpr-DDB1 interaction in apoptosis, DNA repair, and viral replication.

Main Results:

  • Damage-specific DNA-binding protein 1 (DDB1) was identified as a predominant Vpr-interacting protein.
  • Vpr interaction with DDB1 mediates Vpr-induced apoptosis and degradation of UNG2/SMUG1.
  • The Vpr-DDB1 interaction impairs the repair of UV-damaged DNA, contributing to G2 arrest and apoptosis.

Conclusions:

  • The interaction between HIV-1 Vpr and DDB1 is crucial for Vpr-mediated apoptosis, UNG2/SMUG1 degradation, and impaired DNA repair.
  • This interaction likely explains several diverse biological functions of Vpr.
  • The Vpr-DDB1 interaction suggests potential roles for Vpr in HIV-1 replication.

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