Reovirus Activates a Caspase-Independent Cell Death Pathway

Berger, Angela K.; Danthi, Pranav

Though reovirus-induced cell death has been extensively examined in a variety of cell lines (8, 20, 30-34, 49, 55-57) , this is the first demonstration of necroptosis following reovirus infection. One possible reason for why this observation has not been previously reported is that prior studies on reovirus apoptosis, including our own, have not examined this possibility. In the majority of studies, cell death following reovirus infection has been considered apoptotic due to the presence of morphological and biochemical features, but the effect of treatments that block cell death has been evaluated in some (8, 14, 32, 58) but not all (27) (28) (29) (30) (31) 51) cell types. Alternatively, it is possible that this pathway has been discovered in L929 cells due to peculiarities in the amounts or activities of proteins that regulate various forms of cell death. Because L929 cells are among the most permissive to reovirus infection, a related possibility is that reovirus alters the levels of these signaling or regulatory molecules differently or to a different extent than in other cell types. Regardless, our data indicate that necroptosis following reovirus infection is an alternate mechanism of cell death.