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

We have compared the antiviral activity of 20 porcine IFN peptides family-wide. Compared with typical subtypes of porcine type I and III IFNs including IFN-α and -β, IFN-ω exerted most broad antiviral activity. Using VSV and PRRSV, we previously reported that in porcine and monkey cells, most IFN-α peptides showed high antiviral activity on average (9, 13) . Interestingly, IFN-ω peptides exert broad antiviral activity including IFN-ω1 to IFN-ω2 having generally low to mid antiviral activity, and IFN-ω5 (particularly, polymorphic mutant of IFNω5-2 in Figure 3 ) exerting the highest antiviral activity. Other subtypes, including IFN-β and most IFN-δ induced much lower antiviral activity (9, 13) . In Figure 9 , we further compared antiviral activity of porcine IFN-α1, IFN-ω1, and IFN-ω5 against PRRSV (a type II P129 strain) and several strains of influenza A virus (pH1N1, WSN, and K07 strain) in corresponding porcine, mouse and primate cells that are susceptible to the indicated virus infection. IFN-α1 generally had an activity at 10 3 -10 4 U/µg/ml against PRRSV in porcine and MARC-145 cells, but had little activity against influenza viruses in human and mouse cells. In contrast, IFN-ω1 and particularly IFN-ω5, were broadly and highly active against both PRRSV and influenza viruses in cells from the four mammalian species. In all eight types of virus-cell infection systems, IFN-ω5 exerted the highest antiviral activity (100-1,000-fold higher than IFN-α1) for PRRSV and influenza viruses (Figure 9 ).