Designing and building oncolytic viruses

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

Beyond the step of cell entry, viruses are exquisite sensors of intracellular processes and can therefore be adapted or engineered in several ways for intracellular targeting of cancer cells. This is best understood by considering some fundamental aspects of the interplay between a virus and an infected cell. The incoming virus aims to usurp the cellular synthetic machinery for generation of progeny viruses. The cell resists this takeover bid by rapidly detecting virus invasion, then triggering a signaling cascade that leads to establishment of an antiviral state and release of interferon which induces an anti viral state in adjacent cells [105, 106] . The antiviral state is very complex but suppression of protein translation is a key component. Apoptosis is also triggered by the virus detection machinery so that the infected cell dies before it is able to manufacture virus progeny [107] .