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

The majority of IFN studies have concentrated on the induced expression of classical antiviral IFN-α/β responding to viral infection or treatments with viral mimics (1) (2) (3) (4) (5) (6) (7) . Recent studies highlighted the tissue-specific expression of unconventional IFN subtypes such as IFN-λ in gut epithelia, IFN-κ in skin, and IFN-ε/τ in reproductive tract (5, 15, 31, 32) . Thus, more genespecific expression analyses need to be developed to determine potential tissue-or even cell-specific expression of the expanding unconventional IFN subtypes (such as IFN-δ/τ /ω in pigs and cattle) to elucidate functional characterization of these lessstudied IFN subtypes. In addition, recent studies of the multifunctional property of unconventional IFNs also propose that IFNs can mediate immune or other physiological responses via non-canonical signaling pathways including that by intracellular IFN-signaling independent of membrane-bound IFNAR and through MAPK-and PI3K-mediated pathways independent to STAT transcription factors (4, 23, (37) (38) (39) (40) (41) . Currently, direct evidence to determine if some IFN-ω may adopt these noncanonical signaling pathways to mediate subtype-specific IFN responses is lacking; however, our discovery of their differential biological responses in antiviral, anti-proliferation, and ISG induction, especially the lack of a signal peptide for extracellular secretion, all imply this possibility (4, 23, (37) (38) (39) (40) (41) .