Porcine type I interferons: polymorphic sequences and activity against PRRSV

Abstract

Background: Type I interferons (IFN) are a heterogeneous group of cytokines central to innate and adaptive antiviral immune responses. We have recently reported that porcine type I IFNs comprise at least 39 functional genes with diverse antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). Here we report that potential cytokine polymorphisms exist in several genes of porcine type I IFNs. Results: We have detected more than 100 potential polymorphic mutations, which include nucleotide substitutions and deletions, within the coding regions of porcine type I IFNs. Approximately 50% of the nucleotide changes were mutations that resulted in non-conserved amino acid substitution, as well as deletions that produced frame shifts in the open reading frames (ORFs). We have identified more than 20 polymorphic mutants that showed alterations in anti-PRRSV and anti-vesicular stomatitis virus (VSV) activity in vitro. In particular, some mutations in IFN-α2, IFN-α3, IFN-α8, IFN-α12 and IFN-ω5 significantly altered the antiviral activity of expressed proteins in comparison to the wild-type or variant with more similarity to the wild-type. Conclusions: Multiple polymorphic isoforms potentially exist within subtypes of the porcine type I IFN family. Polymorphic mutations are more common in multiple-member subtypes than single-member subtypes, and most are found within the IFN-α subclass. Some polymorphic isoforms have altered amino acid composition and shifted ORFs, which show significantly different antiviral activity in vitro.