Reovirus Activates a Caspase-Independent Cell Death Pathway

Berger, Angela K.; Danthi, Pranav

To determine if genomic dsRNA is sufficient to trigger necroptosis, we assessed the capacity of UV-inactivated virus to evoke cell death. UV-inactivated reovirus contains genomic dsRNA, but the RNA is not competent to serve as a template for viral mRNA synthesis. We observed that UV-treated reovirus particles had a significantly lower capacity for inducing cell death than an equivalent dose of infectious virus (Fig. 5B) . These findings indicate that genomic dsRNA within incoming virus particles is insufficient to evoke necroptosis in infected cells and suggest that de novo synthesis of viral RNA is required for induction of necroptosis following reovirus infection. Since viral genomic RNA and virus replication are dispensable for induction of apoptosis (19, 49) , these findings suggest that apoptosis and necroptosis following reovirus infection are initiated at different stages of viral infection.