PDF(Pubmed)
Abstract：
Type I interferon (IFN) response is the first line of host-based innate immune defense against viral infections. However, viruses have developed multiple strategies to counter host IFN responses, so they may continue infecting hosts via effective replication. Avian reovirus (ARV), an RNA virus, causes viral arthritis or tenosynovitis in chickens. Previous studies have shown that ARV is highly resistant to the antiviral effects of IFN. However, the underlying mechanisms that enable ARV to block the IFN pathway remain unclear. In this study, we found that ectopic expression of ARV protein, σA, significantly inhibited the production of IFN-β induced by melanoma-differentiation-associated gene 5 (MDA5) and poly(I·C). Knockdown of σA during ARV infection enhances the IFN-β response and suppresses viral replication. ARV σA inhibited the MDA5-mediated IFN-β activation by targeting interferon regulatory factor 7 (IRF7). Further studies demonstrated that σA interacts with IRF7, thereby blocking IRF7 dimerization and nuclear translocation, finally leading to the inhibition of IFN-β production. These findings reveal a novel mechanism that allows ARV to evade host antiviral immunity. IMPORTANCE ARV, the causative agent of viral arthritis or tenosynovitis in chickens, has a significant economic impact as it results in poor weight gain and increased feed conversion ratios. The MDA5-mediated IFN-β signal pathway plays an important role in host antiviral defense. Therefore, RNA viruses have developed mechanisms to counter this signaling pathway and successfully establish infection. However, the strategies adopted by ARV to block MDA5-IRF7 signaling remain unclear. In the current study, we demonstrated that ARV σA inhibits this pathway by binding to IRF7, which blocked IRF7 dimerization and nuclear translocation. Our findings may provide insights into how avian reovirus counteracts the innate antiviral immunity of the host to ensure viral replication.
摘要：
I型干扰素(IFN)应答是针对病毒感染的基于宿主的先天免疫防御的第一线。然而,病毒已经开发了多种策略来对抗宿主IFN反应，所以他们可以通过有效的复制继续感染主机。禽呼肠孤病毒(ARV),RNA病毒,引起鸡的病毒性关节炎或腱鞘炎。先前的研究表明，ARV对IFN的抗病毒作用具有高度抗性。然而,ARV阻断IFN途径的潜在机制尚不清楚.在这项研究中,我们发现ARV蛋白的异位表达，σA,显着抑制黑色素瘤分化相关基因5（MDA5）和poly（I·C）诱导的IFN-β的产生。在ARV感染期间σA的敲低增强IFN-β应答并抑制病毒复制。ARVσA通过靶向干扰素调节因子7(IRF7)抑制MDA5介导的IFN-β活化。进一步的研究表明，σA与IRF7相互作用，从而阻断IRF7二聚化和核易位，最终导致IFN-β产生的抑制。这些发现揭示了一种使ARV逃避宿主抗病毒免疫的新机制。IMPORTANCEARV,鸡病毒性关节炎或腱鞘炎的病原体，具有显著的经济影响,因为其导致差的重量增加和增加的饲料转化率。MDA5介导的IFN-β信号通路在宿主抗病毒防御中起重要作用。因此,RNA病毒已经开发出对抗这种信号通路并成功建立感染的机制。然而,ARV阻断MDA5-IRF7信号传导的策略尚不清楚.在目前的研究中,我们证明ARVσA通过与IRF7结合来抑制该途径，从而阻断IRF7二聚化和核易位。我们的发现可以提供有关禽呼肠孤病毒如何抵消宿主的先天抗病毒免疫以确保病毒复制的见解。
