A ubiquitin-specific protease possesses a decisive role for adenovirus replication and oncogene-mediated

Wilhelm Ching1, Emre Koyuncu, Sonia Singh

  • 1Department of Molecular Virology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

Plos Pathogens
|April 5, 2013
PubMed

Insights

Researchers found that the deubiquitinating enzyme USP7 is crucial for adenovirus replication and oncogenic functions. Inhibiting USP7 significantly reduces viral replication and cellular transformation, suggesting new antiviral strategies.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Adenoviral replication relies on both viral and cellular proteins.
  • The roles of cellular proteins in promoting adenoviral replication are not well understood.

Purpose of the Study:

  • To identify cellular proteins that promote adenoviral replication.
  • To investigate the interaction between adenoviral proteins and cellular factors.
  • To explore USP7's role in adenoviral replication and oncogenesis.

Main Methods:

  • Protein interaction assays to map binding domains between viral E1B-55K and USP7.
  • RNA interference (RNAi) to downregulate USP7 expression.
  • Synthesis and application of a USP7 inhibitor.
  • Assays to measure adenoviral replication and cellular transformation.

Main Results:

  • A specific interaction was identified between adenoviral E1B-55K and the deubiquitinating enzyme USP7.
  • Downregulation of USP7 led to reduced E1B-55K protein levels and severely impaired adenoviral replication.
  • USP7 inhibition also reduced adenoviral replication and oncogene-driven cellular transformation.
  • Adenoviral replication and oncogenic functions depend on USP7 activity.

Conclusions:

  • USP7 is a critical cellular factor usurped by adenovirus for replication and oncogenic functions.
  • Targeting USP7 presents a potential strategy for developing new antiviral therapies against adenoviruses.

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