Abstract
Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-α/-β and IFN-λ, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activation and annexin-V detection. The apoptosis response was inhibited by B18R protein (a type I IFN inhibitor) in tumor cells i.e. A549 and U87MG, and not in normal cells i.e. NB1RGB and HEK293. Similarly, UV-inactivated medium from NDV infection was shown to induce apoptosis in corresponding cells and the response was inhibited in A549 and U87MG cells with the addition of B18R protein. Treatment with combination of IFNs-α/-β/-λ or IFNs-α/-β or IFN-λ in NB1RGB, HEK293, A549 and U87MG showed that caspase activity in IFNs-α/-β/-λ group was the highest, followed with IFN-α/-β group and IFN-λ group. This suggests that tumor-selectivity of NDV is mainly because of the cumulative effect of type I and III in tumor cells that lead to higher apoptotic effect.