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A capsid-encoded PPxY-motif facilitates adenovirus entry

Harald Wodrich1, Daniel Henaff, Baptist Jammart

  • 1Institut Génétique Moléculaire de Montpellier, Montpellier, France. harald.wodrich@u-bordeaux2.fr

Plos Pathogens
|March 25, 2010
PubMed

Insights

Adenoviruses (Ads) use protein VI

Area of Science:

  • Virology, Cell Biology, Molecular Biology

Background:

  • Viruses rely on host cellular machinery for infection.
  • Understanding nonenveloped adenovirus (Ad) cell entry is crucial for antiviral strategies.

Purpose of the Study:

  • To investigate the role of protein VI and its PPxY motif in Ad cell entry and intracellular trafficking.

Main Methods:

  • Analysis of protein VI exposure and association with the capsid.
  • Investigating the interaction between protein VI's PPxY motif and Nedd4 E3 ubiquitin ligases.
  • Assessing the impact of PPxY motif mutations and Nedd4 ligase depletion on Ad trafficking and infection.

Main Results:

  • Protein VI is exposed early in entry and recruits Nedd4 ligases via its PPxY motif.
  • The PPxY motif is essential for rapid, microtubule-dependent intracellular transport of Ads.
  • Mutations in the PPxY motif or depletion of Nedd4 ligases impair nuclear accumulation and infection.

Conclusions:

  • Virus-encoded PPxY motifs are critical for efficient Ad cell entry and nuclear targeting.
  • This mechanism highlights a novel role for ubiquitylation in viral intracellular trafficking.
  • Findings may extend to other pathogens utilizing similar entry strategies.

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