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Updated: Jun 2, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
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.
Abstract:
Adenoviruses with deletion of E1b have been used in clinical trials to treat cancers that are resistant to conventional therapies. The efficacy of viral replication within cancer cells determines the results of oncolytic therapy, which remains poorly understood and requires further improvement. In this report, we show that adenoviruses induce autophagy by increasing the conversion of LC3-I to LC3-II and the formation of the Atg12-Atg5 complex. Inhibition of autophagy with 3-methyladenine (3MA) resulted in a decreased synthesis of adenovirus structural proteins, and thereby a poor viral replication; promotion of autophagy with rapamycin increased adenovirus yield. This study indicates that adenovirus-induced autophagy correlates positively with virus replication and oncolytic cell death, and that autophagy may generate nutrients that can be used for building viral progeny particles. These results further suggest that chemotherapeutic agents that increase cancer cell autophagy may improve the efficacy of oncolytic virotherapy.
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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