Reovirus Activates a Caspase-Independent Cell Death Pathway

Berger, Angela K.; Danthi, Pranav

tutes an intrinsic response of the host cell to viral infection (1, 2) . Though both apoptosis and necrosis function to limit viral infection, they each have markedly different effects on the cell. While apoptosis results in membrane blebbing, nuclear condensation, and DNA fragmentation, the integrity of the plasma membrane is maintained (3) . In contrast, necrosis results in cell rounding, cell swelling, and ultimately a loss of plasma membrane integrity, leading to the leakage of host cytoplasmic contents (3) . In addition to the morphological differences in dying cells, apoptosis and necrosis also influence host physiology in a distinct manner. While cells dying by apoptosis do not activate the immune system, the leakiness of necrotic cells recruits immune cells and promotes inflammation (4), potentially enhancing pathology associated with cell death. Though necrosis was generally considered to be an unregulated, uncontrolled form of cell death, recent evidence indicates that at least one form of necrosis, necroptosis, is programmed (5) . In addition to the leakiness of membranes observed in all forms of necrosis, necroptosis is characterized by the activation of signaling from death receptors, the dispensability of caspase activity, and a requirement for the kinase activity of recep-tor interacting protein 1 (RIP1 or RIPK1) or 3 (RIP3 or RIPK3) (3) . Though both apoptosis and necroptosis have been shown to occur during viral infection, it is not known if similar events in viral infection trigger apoptosis and necroptosis (1) . Conditions that favor one form of cell death over the other during viral infection are also not understood.