Whole Transcriptome of Frog virus 3-Infected Xenopus laevis

The immunome is the set of genes and proteins that constitute the immune system. Interferons (IFNs) are key cytokines that mark immune adaptation and critically mediate antitumor and antiviral immunity in jawed vertebrates. One long-term objective of this project is to understand the signature role of amphibian IFN complex in IFN evolution and functional diversification in vertebrates. Similar to adaptive immunity, IFNs also originate in jawed fish from the multi-exon progenitors. The evolution of intronless (or single-exon) IFN genes and further molecular diversification in amniotes are signature events in immune evolution. Recent research detected the unexpected emergence and expansion of intronless IFN genes in amphibians, exemplified by 40-50 functional IFN genes, of which 24-37 are intronless in each Xenopus species. This remarkable coexistence of intron-containing and intronless IFN genes in amphibians confirms that the emergence and first expansion of intronless IFN genes actually occurred earlier in amphibians rather than the previously believed reptiles. This discovery revises the established model of IFN evolution and highlights that amphibians are critical in studying IFN biology in vertebrates. Functional characterization of amphibian IFN immunome is fundamental to directly addressing the infectious challenges that are causing current amphibian declines, and will update immunobiology in vertebrates. We proposes to functionally study amphibian IFN immunome, especially the intronless IFNs, in order to examine their homeostatic role during development and antiviral regulation in a ranaviral infection. The hypothesis of this proposal is that the molecular emergence and expansion of the amphibian IFN complex confer functional diversification through regulating the canonical IFN-signaling pathway, which provides a unique and previously unknown platform to address IFN evolution, functional capacity, and especially amphibian defense against viral infections.