Department of Population Health and Reproduction, University of California, Davis, Davis, CA 95616, USA.
Mol Immunol. 2013 Dec;56(4):358-68. doi: 10.1016/j.molimm.2013.05.236. Epub 2013 Aug 1.
The NS1 gene encoded by Type A influenza virus circulates as two alleles, the A and B allele. The immunomodulatory properties of the NS1 A allele have been thoroughly examined; however, comparisons of allele function have been predominantly made in mammalian systems. Here we show that counter to the current understanding of allele function in mammals, the two alleles similarly regulate elements of the type I interferon (IFN) signaling pathway, including the interferon-inducible genes Mx and 2'-5' oligoadenylate synthase (2'-5' OAS), and IL-6, which share the same induction pathway as the interferons in embryo fibroblasts from chickens, turkeys or ducks. Replication of two reassortant viruses demonstrated that the B allele virus replicates more and to higher titers than the A allele virus in duck cells; however, the A allele virus replicates more in the cells from chickens and turkeys. Finally, chimeric constructs were used to identify a region of the NS1 gene that conferred the statistically significant differences in expression and replication observed between the alleles.
A型流感病毒的 NS1 基因编码两种等位基因，即 A 等位基因和 B 等位基因。NS1 A 等位基因的免疫调节特性已被深入研究；然而，等位基因功能的比较主要是在哺乳动物系统中进行的。在这里，我们表明与目前在哺乳动物中对等位基因功能的理解相反，这两个等位基因相似地调节 I 型干扰素 (IFN) 信号通路的元件，包括干扰素诱导基因 Mx 和 2'-5'寡聚腺苷酸合成酶 (2'-5' OAS)，以及 IL-6，它们在鸡、火鸡或鸭的胚胎成纤维细胞中与干扰素共享相同的诱导途径。两种重配病毒的复制表明，在鸭细胞中，B 等位基因病毒的复制比 A 等位基因病毒更多且滴度更高；然而，A 等位基因病毒在来自鸡和火鸡的细胞中复制更多。最后，使用嵌合构建体来鉴定 NS1 基因的一个区域，该区域赋予了在等位基因之间观察到的表达和复制的显著差异。
