Exploring Host Factors that Impact Reovirus Replication, Dissemination, and Reovirus-Induced Cell Death in Cancer Versus Normal Cells in Culture

Oncolytic viruses, such as reovirus, offer a promising approach to cancer treatment. Concurrently, oncolytic viruses provide a valuable tool for deciphering unique attributes of cancer cells that support superior virus replication, cell death, or virus dissemination. Through our studies on various cancer cell lines, as well as isogenic cells with and without transformation by oncogenic Ras, we have identified at least four steps of virus replication that can be augmented in transformed cells. Ras transformation can support efficient reovirus uncoating during entry, production of progeny with high infectious capacity, and reovirus-induced apoptosis. Furthermore, Ras transformation also precludes interferon production following reovirus infection, permitting enhanced cell-to-cell virus spread. Methods that measure the efficiency of reovirus replication and dissemination described in this chapter can be used in combination with assorted cell culture systems to better understand the host factors that regulate reovirus oncolysis.