Abstract：
RLR helicases RIG-I and MDA5, which are known as pattern recognition receptors to sense cytoplasmic viral RNAs and trigger antiviral immune responses, are DExD/H-box helicases. In teleost, whether and how non-RLR helicases regulate RLR helicases to affect viral infection remains unclear. Here, we report that the non-RLR helicase DHX40 from grass carp (namely gcDHX40) is a negative regulator of grass carp reovirus (GCRV) infection and RLR-mediated type I IFN production. GcDHX40 was a cytoplasmic protein. Ectopic expression of gcDHX40 facilitated GCRV replication and suppressed type I IFN production induced by GCRV infection and by those genes involved the RLR antiviral signaling pathway. Mechanistically, gcDHX40 promoted the generation of viral inclusion bodies (VIBs) by interacting with the NS38 protein of GCRV. Additionally, gcDHX40 interacted with RLR helicase, and impaired the formation of RLR-MAVS functional complexes. Taken together, our results indicate that gcDHX40 is a novel important proviral host factor involving in promoting the generation of GCRV VIBs and inhibiting the production of RLR-mediated type I IFNs.
摘要：
RLR解旋酶RIG-I和MDA5，它们被称为模式识别受体，用于感知细胞质病毒RNA并触发抗病毒免疫反应。是DExD/H盒解旋酶。在teleost,非RLR解旋酶是否以及如何调节RLR解旋酶以影响病毒感染尚不清楚.这里,我们报告说，来自草鱼的非RLR解旋酶DHX40（即gcDHX40）是草鱼呼肠孤病毒（GCRV）感染和RLR介导的I型IFN产生的负调节因子。gcDHX40是细胞质蛋白。gcDHX40的异位表达促进GCRV复制，并抑制由GCRV感染诱导的I型IFN产生，这些基因涉及RLR抗病毒信号通路。机械上,gcDHX40通过与GCRV的NS38蛋白相互作用促进病毒包涵体(VIBs)的产生。此外,gcDHX40与RLR解旋酶相互作用，并损害了RLR-MAVS功能复合物的形成。一起来看,我们的结果表明，gcDHX40是一种新的重要的前病毒宿主因子，参与促进GCRVVIBs的产生和抑制RLR介导的I型IFN的产生。
