PDF(Pubmed)
Abstract：
Enterovirus D68 (EV-D68) primarily spreads through the respiratory tract and causes respiratory symptoms in children and acute flaccid myelitis (AFM). Type III interferons (IFNs) play a critical role in inhibiting viral growth in respiratory epithelial cells. However, the mechanism by which EV-D68 induces type III IFN production is not yet fully understood. In this study, we show that EV-D68 infection stimulates Calu-3 cells to secrete IFN-λ. The transfection of EV-D68 viral RNA (vRNA) stimulated IFN-λ via MDA5. Furthermore, our findings provide evidence that EV-D68 infection also induces MDA5-IRF3/IRF7-mediated IFN-λ. In addition, we discovered that EV-D68 infection downregulated MDA5 expression. Knockdown of MDA5 increased EV-D68 replication in Calu-3 cells. Finally, we demonstrated that the IFN-λ1 and IFN-λ2/3 proteins effectively inhibit EV-D68 infection in respiratory epithelial cells. In summary, our study shows that EV-D68 induces type III IFN production via the activated MDA5-IRF3/IRF7 pathway and that type III IFNs inhibit EV-D68 replication in Calu-3 cells.
摘要：
肠道病毒D68（EV-D68）主要通过呼吸道传播，并在儿童和急性弛缓性脊髓炎（AFM）中引起呼吸道症状。III型干扰素（IFN）在抑制呼吸道上皮细胞中的病毒生长中起关键作用。然而,EV-D68诱导III型IFN产生的机制尚不完全清楚。在这项研究中,我们显示EV-D68感染刺激Calu-3细胞分泌IFN-λ。EV-D68病毒RNA(vRNA)的转染通过MDA5刺激IFN-λ。此外，我们的研究结果提供了证据，即EV-D68感染也诱导MDA5-IRF3/IRF7介导的IFN-λ。此外,我们发现EV-D68感染下调MDA5的表达。敲除MDA5增加了Calu-3细胞中的EV-D68复制。最后,我们证明了IFN-λ1和IFN-λ2/3蛋白有效抑制呼吸道上皮细胞中的EV-D68感染。总之,我们的研究表明，EV-D68通过激活的MDA5-IRF3/IRF7途径诱导III型IFN的产生，而III型IFN抑制Calu-3细胞中EV-D68的复制。
