RNA viruses as virotherapy agents.

Abstract

RNA viruses are rapidly emerging as extraordinarily promising agents for oncolytic virotherapy. Integral to the lifecycles of all RNA viruses is the formation of double-stranded RNA, which activates a spectrum of cellular defense mechanisms including the activation of PKR and the release of interferon. Tumors are frequently defective in their PKR signaling and interferon response pathways, and therefore provide a relatively permissive substrate for the propagation of RNA viruses. For most of the oncolytic RNA viruses currently under study, tumor specificity is either a natural characteristic of the virus, or a serendipitous consequence of adapting the virus to propagate in human tumor cell lines. Further refinement and optimization of these oncolytic agents can be achieved through virus engineering. This article provides a summary of the current status of oncolytic virotherapy efforts for seven different RNA viruses, namely, mumps, Newcastle disease virus, measles virus, vesicular stomatitis virus, influenza, reovirus, and poliovirus.