Synthetic long double-stranded RNA induces apoptosis in the sea anemone Nematostella vectensis

Programmed cell death (apoptosis) is an essential component of host defense against invading intracellular pathogens. Particularly, apoptosis is important for limiting pathogen replication in infected cells, while simultaneously promoting the inflammatory and innate responses that are crucial for host immunity. Dysregulation of cell death as a result of defects in the apoptotic pathways is often a characteristic of inflammatory, autoimmune disorders and cancer. Moreover, many viruses encode inhibitors of apoptosis to evade host responses during infection, and to support their own replication and survival. Until now, apoptosis in the context of the antiviral immune system has been almost exclusively studied in vertebrates. This limited phyletic sampling makes it impossible to determine whether a similar mechanism existed in the last common ancestor of animals. Here, we established assays to probe apoptosis in the sea anemone Nematostella vectensis, a representative model species of Cnidaria, a phylum that diverged approximately 600 million years ago from the rest of animals. We show that polyinosinic:polycytide (poly I:C), a synthetic long double-stranded sRNA mimicking viral RNA and a primary ligand for the vertebrate RLR melanoma differentiation-associated protein 5 (MDA5), is sufficient to induce apoptosis in Nematostella. Furthermore, to test whether induction of apoptosis by a viral mimic is functionally conserved, we will use genetic manipulation to determine the role of the MDA5 ortholog in Nematostella in regulating this process.