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Porcine type I interferons: polymorphic sequences and activity against PRRSV

机译:猪I型干扰素:多态性序列和针对PRRSV的活性

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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 .
机译:背景技术I型干扰素(IFN)是异源性细胞因子组,对先天性和适应性抗病毒免疫反应至关重要。最近,我们报道了猪I型干扰素包含至少39个功能基因,这些基因具有针对猪繁殖与呼吸综合征病毒(PRRSV)的多种抗病毒活性。在这里我们报告潜在的细胞因子多态性存在于猪I型干扰素的几个基因中。结果我们已经在猪I型IFN的编码区内检测到100多个潜在的多态性突变,包括核苷酸取代和缺失。大约50%的核苷酸变化是导致非保守氨基酸取代的突变,以及在开放阅读框(ORF)中产生移码的缺失。我们已经鉴定出20多个多态性突变体,它们在体外显示出抗PRRSV和抗水泡性口炎病毒(VSV)活性的变化。特别地,与野生型或与野生型更相似的变体相比,IFN-α2,IFN-α3,IFN-α8,IFN-α12和IFN-ω5的某些突变显着改变了表达蛋白的抗病毒活性。 。结论猪I型IFN家族亚型内可能存在多种多态同工型。多态突变在多成员亚型中比单成员亚型更常见,并且大多数在IFN-α亚类中发现。一些多晶型同工型改变了氨基酸组成并改变了ORF,在体外显示出明显不同的抗病毒活性。

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