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 addition to the major clusters of the unconventional IFN subtypes in livestock, we also detected some "outliers" per molecular signatures. For example, porcine IFN-δ1, -δ2, and -ω2, as well as bovine IFN-ω4 (Bb), -ω6 (Bt), -ω14 (Bb), -ω22 (Bt) show less sequence identity (<80%) overall to other members of the same IFN subtypes (Figures 2, 4) . As these members generally showed little antiviral activity in all our tests (9, 13, 23), we also detected that these "outliers" of the unconventional IFN subtypes generally do not contain signal peptides for extracellular secretion of the mature IFN peptides (Figure 10 ) (10, 37) . This indicates that these "outliers" may represent a group of IFNs that mediate IFN responses via a newly identified intracellular pathway (10, 37) , or a non-canonical IFN signaling pathway to mediate some unknown functions (10, (37) (38) (39) .