Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-? Subtype

Shields, Lauren E.; Jennings, Jordan; Liu, Qinfang; Lee, Jinhwa; Ma, Wenjun; Blecha, Frank; Miller, Laura C.; Sang, Yongming

In summary, genome-wide annotation of the IFN complex across more than 110 representative species of vertebrates allows us to extensively re-examine the IFN evolutionary model (2, 10, 40) , which serves as a critical molecular marker for immune evolution simultaneous to emergence of adaptive immunity in vertebrates (45) . Our extensive phylogenic analyses refined several "turning-points" in IFN evolution, including the emergence and expansion of intronless IFN genes in amphibians as well as further IFN-subtype diversification surge in bats and especially in ungulate species (2, (8) (9) (10) (11) (12) . Furthermore, we emphasize the necessity for molecular and functional characterization of unconventional IFN subtypes using several animal models, which show significant IFN expansion thus providing molecular resource for identifying and optimizing "super" IFNs for therapeutic application in either antiviral or immunomodulatory directions (3, 18, 19) . We propose using the porcine IFN model, that unconventional IFN subtypes such as IFN-ω are promising for developing IFN-based antivirals that exert antiviral activity superior to classical IFNα/β subtypes, which stresses the multi-functional property of IFN cytokines beyond the several well-studied subtypes and calls for mechanistic studies of the non-canonical IFN signaling pathways (4, (37) (38) (39) (40) (41) .