Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus

Ranaviruses (Iridoviridae) are posing an increasing threat to amphibian populations, with anuran tadpoles being particularly susceptible to these viral infections. Moreover, amphibians are the most basal phylogenetic class of vertebrates known to possess both type I and type III interferon (IFN)-mediated immunity. Moreover, little is known regarding the respective roles of the IFN mediators in amphibian antiviral defenses. Accordingly, we transcriptionally and functionally compared the amphibian Xeno-pus laevis type I (IFN) and III (IFN-) IFNs in the context of infections by the ranavirus frog virus 3 (FV3). X. laevis IFN and IFN- displayed distinct tissue expression profiles. In contrast to our previous findings that X. laevis tadpoles exhibit delayed andmodest type I IFN responses to FV3 infections compared to the responses of adults, here we report that tadpoles mount timely and robust type III IFN gene responses. Recombinant forms of these cytokines (recombinant X. laevis IFN [rXlIFN] and rXlIFN-) elicited antiviral gene expression in the kidney-derived A6 cell line as well as in tadpole leukocytes and tissues. How-ever, rXlIFN-was less effective than rXlIFN in preventing FV3 replication in A6 cells and tadpoles and inferior at promoting tadpole survival. Intriguingly, FV3 impaired A6 cell and tadpole kidney type III IFN receptor gene expression. Furthermore, in A6 cultures rXlIFN- conferred equal or greater protection than rXlIFN against recombinant viruses deficient for the putative immune evasion genes, the viral caspase activation and recruitment domain (vCARD) or a truncated vIF-2 gene. Thus, in con-trast to previous assumptions, tadpoles possess intact antiviral defenses reliant on type III IFNs, which are overcome by FV