Reovirus infection reduces the expression of NKG2D-ligands on tumor cells leading to impaired activating signal of the NKG2D-receptor of NK cells

In recent years, reovirus has been of major interest in cancer research due to its oncolytic properties. Using the rat sarcoma virus (RAS) machinery, reovirus can replicate inside and lyse tumor cells, while leaving healthy cells intact. Yet, little is known about how reovirus infection affects the activity of natural killer (NK)cells, a major tumor cell-eliminator. Towards this end, we tested how reovirus affects the activating signal of NK Group 2D (NKG2D) receptor (NKG2D-R), which binds to several stress-induced ligands present on the cell membrane. By using U87-MG and MNT-1 cells as a model for human-derived tumor, we measured the expression of NKG2D-ligands on the cell-membrane post reovirus infection, and the binding of NKG2D-recepotor to infected cells. We demonstrated that NKG2D-ligands are down-regulated post reovirus-infection. We also showed that NKG2D-receptor binding to tumor cells is impaired following infection. Additionally, we showed that the effect seems to be due to impaired translation of the NKG2D-ligands. Currently, we aim on identifying the mechanism in which reovirus affects NKG2D-ligands expression. Altogether, this research provides novel insights on reovirus-host interaction and could lead to the development of novel therapeutics that will better eliminate tumor cells.