Adenoviruses induce autophagy to promote virus replication and oncolysis

Humberto Rodriguez-Rocha1, Jorge G Gomez-Gutierrez, Aracely Garcia-Garcia

  • 1Department of Surgery, University of Louisville School of Medicine, KY 40292, USA.

Virology
|May 18, 2011
PubMed

Insights

Adenoviruses induce autophagy, a cellular process that aids their replication. Enhancing autophagy boosts viral yield and oncolytic cancer therapy effectiveness, suggesting new treatment strategies.

Area of Science:

  • Oncolytic virotherapy
  • Cellular biology
  • Cancer research

Background:

  • Adenoviruses lacking E1b are used in clinical trials for cancer treatment.
  • The efficacy of oncolytic virotherapy depends on viral replication within cancer cells.
  • Understanding viral replication mechanisms is crucial for improving oncolytic therapy outcomes.

Purpose of the Study:

  • To investigate the role of autophagy in adenovirus replication.
  • To determine the correlation between autophagy and oncolytic virotherapy efficacy.

Main Methods:

  • Adenoviruses were used to infect cancer cells.
  • Autophagy was modulated using 3-methyladenine (3MA) to inhibit and rapamycin to promote the process.
  • Levels of LC3-I to LC3-II conversion and Atg12-Atg5 complex formation were measured.
  • Adenovirus replication and protein synthesis were quantified.

Main Results:

  • Adenoviruses were found to induce autophagy, evidenced by increased LC3-II and Atg12-Atg5 complex formation.
  • Inhibition of autophagy with 3MA significantly reduced viral replication and protein synthesis.
  • Promotion of autophagy with rapamycin enhanced adenovirus yield.
  • A positive correlation was observed between adenovirus-induced autophagy, viral replication, and oncolytic cell death.

Conclusions:

  • Adenovirus-induced autophagy is a key factor supporting viral replication.
  • Autophagy likely provides essential nutrients for the production of new viral particles.
  • Targeting cancer cell autophagy could enhance the effectiveness of oncolytic virotherapy.

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