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

me recombinant feline IFN-ω peptides have been licensed in several countries for treating canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections (18, 42) , indicating the broad antiviral potency and therapeutic potentials of this unconventional IFN subtype (13, 19, 20) . Others and we have genome-wide analyzed the superior IFN complex in ungulate species especially in pigs and cattle (8, 9) , indicating that these livestock species contain the IFN complex including IFN-ω subtype which may conceive distinct IFN molecules having higher antiviral or other biological activity. In addition to these genetically fixed IFN alleles, we have also identified many polymorphic isoforms across the porcine type I IFN gene family (14, 29) , of which some differ by only one or a few residues but exert dramatic antiviral alterations, such as by different IFN-ω variants (Figure 3 ) (14, 29) . Indeed, such as those among seven porcine IFN-ω5 isoforms, we determined a polymorphism (IFN-ω5-2, Figure 3 ) that has much higher antiviral activity broadly in all our analyses including seven different virus-cell systems (Figure 9 ) (14, 19) . This correlates with the seminal discovery of structure-activity relationship of IFN site-mutants by Thomas et al. (29) and indicates the efficacy of "fine-tuning" approaches in optimization of IFN biology activity (29, 43) .