The cnidarian antiviral immune system reflects ancestral complexity in ancient animals

To attain novel insights into the evolution of this the antiviral immune system in animals, we study it in an outgroup: the sea anemone Nematostella vectensis. This animal is a representative of Cnidaria, the phylum that includes sea anemones, corals, jellyfish and hydroids. Cnidarians diverged from Bilateria (the majority of extant animals, including vertebrates, nematodes and insects) 600 million years ago. We harness the genetic and molecular tools available for this species to decipher the cnidarian system for battling RNA viruses and answer the outstanding questions regarding the evolution of antiviral immunity and its ancestral state in animals. We show that like bilaterian animals, Nematostella reacts transcriptionally to the viral hallmark of long (200-7000 bp) double-stranded RNA (dsRNA). However, unlike vertebrates and nematodes, Nematostella is not differentially-responsive to short and long dsRNA carrying or lacking the viral hallmark of 5′-triphosphate group. Our transcriptomic results for long dsRNA put in question the textbook dichotomy between the antiviral immune systems of vertebrates and protostomes, as we detect upregulation of interferon-stimulated genes as well as RNA interference components (RNAi) in Nematostella. Furthermore, we show by genetic and biochemical methods that this response is dependent on homologs of classic vertebrate antiviral genes such as RIG-I and MAVS. These findings support an intriguing scenario where the ancient intracellular antiviral innate immunity system which was present in the last common ancestor of Cnidaria and Bilateria was in several aspects more complex and diverse than the systems found in extant vertebrates, arthropods and nematodes.