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

Both species-specific and cross-species activities of IFNs have been reported previously and observed in our studies (2, 18, 20, 42) . Theoretically, IFN activity is determined by the compatibility of an IFN ligand with cell IFN receptors. Due to the evolution of both IFNs and IFN receptors across the vertebrates, typical IFN subtypes such as IFN-α/β show more or less cross-species antiviral activity within each vertebrate groups such as fish, amphibians, reptiles, birds, and mammals. However, the cross-species activity is rare between species of two groups (unpublished data). In contrast, cross-species activity of species-specific IFN subtypes (such as IFN-δ/τ /ξ in pigs, cattle, and mice, respectively) should be limited due to phylogenic distinctness. Whereby, mammalian IFN-ω subtype seems to retain at least antiviral activity within most mammalian species as demonstrated with the single human IFN-ω as well as multiple IFN-ω peptides in cats and pigs (2, 18, 20, 42) . In summary, both species-specific and cross-species IFN activity are two sides of the same coin, which reflects the variation and conservation during IFN evolution (2, 4, 7, 20) .