Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway.
Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway.
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DOI：
10.1016/j.molimm.2008.01.028
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发表时间：
2008-05
影响因子：
3.6
通讯作者：
Fang L
中科院分区：
文献类型：
--
作者：
Luo R;Xiao S;Jiang Y;Jin H;Wang D;Liu M;Chen H;Fang L
猪繁殖与呼吸综合征病毒（PRRSV）是一种经济上重要的猪疾病，自20世纪80年代末以来一直在破坏养猪业。越来越多的证据表明，PRRSV感染不能诱导I型干扰素（IFN-α/β），而在病毒感染的细胞中，这种干扰素通常在病毒复制过程中快速诱导。然而，潜在的机制在很大程度上仍不清楚。在这项研究中，我们发现PRRSV感染激活了NF-κB和AP-1的信号转导成分，但没有激活干扰素调节因子3 (IRF3)，干扰素调节因子是IFN-β的重要转录因子。此外，PRRSV感染显著阻断了合成dsrna诱导的IFN-β产生和IRF3核易位。为了更好地了解抑制IRF3激活的上游信号事件，我们进一步研究了维甲酸诱导基因I （RIG-I）和toll样受体3 （TLR3）介导的信号通路中单个组分在PRRSV感染期间IFN-β产生中的作用。我们观察到PRRSV感染通过灭活rig -1的接头分子IFN-β启动子刺激子1 (IPS-1)，显著抑制dsrna诱导的IRF3激活和IFN-β生成。相比之下，PRRSV感染仅部分降低了含有TIR结构域的接头诱导IFN-β (TRIF)的激活，TRIF是TLR3的接头分子。我们的研究结果表明，PRRSV感染主要通过干扰RIG-I信号通路中的IPS-1激活来抑制IFN-β的产生。
Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has been devastating the swine industry since the late 1980s. Accumulating evidences have revealed that PRRSV infection fails to induce type I interferon (IFN-α/β), which are normally induced rapidly during virus replication in virus-infected cells. However, the potential mechanisms remain largely unclear. In this study, we showed that PRRSV infection activated the signal transduction components of NF-κB and AP-1, but not of interferon regulatory factor 3 (IRF3), an essential IFN-β transcription factor. Furthermore, PRRSV infection significantly blocked synthetic dsRNA-induced IFN-β production and IRF3 nuclear translocation. To better understand the upstream signaling events that suppress IRF3 activation, we further investigated the roles of individual components of the retinoic acid-inducible gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated signaling pathway for IFN-β production during PRRSV infection. We observed that PRRSV infection significantly inhibited dsRNA-induced IRF3 activation and IFN-β generation by inactivating IFN-β promoter stimulator 1 (IPS-1), an adaptor molecule of RIG-I. In contrast, PRRSV infection only partially reduced the activation of TIR domain-containing adaptor inducing IFN-β (TRIF), an adaptor molecule of TLR3. Our results suggest that PRRSV infection suppresses production of IFN-β primarily by interfering with the IPS-1 activation in the RIG-I signaling pathway.
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