Proteolytic Disassembly of Viral Outer Capsid Proteins Is Crucial for Reovirus-Mediated Type-I Interferon Induction in Both Reovirus-Susceptible and Reovirus-Refractory Tumor Cells. (19th March 2015)

• Record Type: Journal Article
• Authors: Katayama, Yuki; Terasawa, Yuichi; Tachibana, Masashi; Mizuguchi, Hiroyuki; Sakurai, Fuminori
• Other Names: Yee Jiing-Kuan Academic Editor.
• Is Part Of: BioMed research international. Volume 2015(2015)
• Publication Date: 2015-03-19
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2015/468457
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Oncolytic reovirus induces innate immune responses, which contribute to the antitumor activity of reovirus, following in vivo application. Reovirus-induced innate immune responses have been relatively well characterized in immune cells and mouse embryonic fibroblasts cells; however, the mechanisms and profiles of reovirus-induced innate immune responses in human tumor cells have not been well understood. In particular, differences in reovirus-induced innate immune responses between reovirus-susceptible and reovirus-refractory tumor cells remain unknown, although the intracellular trafficking of reovirus differs between these tumor cells. In this study, we examined reovirus-induced upregulation of interferon- (IFN-) β and of the proapoptotic gene, Noxa, in reovirus-susceptible and -refractory tumor cells. IFN- β and Noxa were significantly induced by reovirus via the IFN- β promoter stimulator-1 (IPS-1) signaling in both types of tumor cells. Inhibition of cathepsins B and L, which are important for disassembly of reovirus outer capsid proteins and escape into cytoplasm, largely suppressed reovirus-induced upregulation of IFN- β and Noxa expression in not only reovirus-susceptible but also reovirus-refractory tumor cells. These results indicated that in both reovirus-susceptible and reovirus-refractory tumor cells, disassembly of the outer capsid proteins by cathepsins and the escape into the cytoplasm were crucial steps for reovirus-induced innate immunity.