Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-) α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

中文翻译：

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呼吸道合胞病毒非结构蛋白从内源性IFN信号传导以不同的方式上调SOCS1和SOCS3。

呼吸道合胞病毒（RSV）感染会上调细胞因子信号转导（SOCS）家族的基因，该基因利用反馈环抑制I型干扰素依赖性抗病毒信号通路。在这里，我们重组了RSV非结构（NS）蛋白表达质粒（pNS1，pNS2和pNS1 / 2），并测试了NS1或NS2是否会触发SOCS1和SOCS3蛋白表达。这些NS蛋白通过涉及诱导SOCS1和SOCS3的机制来抑制干扰素-（IFN-）α信号传导，这似乎与自分泌IFN依赖性不同。NS1诱导SOCS1和SOCS3上调，而NS2仅诱导SOCS1表达。SOCS1和SOCS3的诱导表达先于内源性IFN信号激活，并抑制IFN诱导的抗病毒反应以及趋化因子诱导。INF-α和NS蛋白处理均可诱导SOCS1表达。但是，它们对依赖于IFN-α的抗病毒基因表达有相反的影响。我们的结果表明，诱导SOCS1或SOCS3表达的NS1和NS2可能代表刺激内源性IFN信号传导的独立途径。