Adenovirus's last trick: You say lysis, we say autophagy

The last stage of the adenovirus replication cycle, lysis, is considered not very efficient and remains poorly understood. Pathogen infection induces autophagy in eukaryotic cells. In the case of viruses, autophagy is a double-edged sword that can either facilitate or impede replication. On one hand, autophagy reduces the replication capability of the herpesviruses. On the other hand, the RNA virus poliovirus uses autophagosomes to form replication complexes. Recently we characterized the autophagy induced by the oncolytic adenovirus Delta-24-RGD in brain tumor stem cells. Late in the adenoviral infectious cycle, we observed remarkable up-regulation of the Atg12-Atg5 complex and prominent autophagy. In addition, adenovirus-induced autophagy results in disruption of the cytoplasmic structure and the continuity of the cellular membrane. We speculate that adenoviruses induce autophagy to facilitate the release of viral progeny at the end of the infectious cycle. The substitution of autophagy for lysis is not just semantic. Because autophagy is a genetically programmed process and not a passive phenomenon, it immediately suggests interactions between adenovirus proteins and autophagy regulators. Understanding the mechanism underlying adenovirus-mediated autophagy should propel the development of novel vectors with enhanced capability to release viral progeny and, as a result, more potent oncolytic effect. Addendum to: Jiang H, Gomez-Manzano C, Aoki H, Alonso MM, Kondo S, McCormick F, Xu J, Kondo Y, Bekele BN, Colman H, Lang FF, Fueyo J. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: Role of autophagic cell death. J Natl Cancer Inst 2007; 99:1410-4.