SVCV infection triggers fish IFN response through RLR signaling pathway
SVCV infection triggers fish IFN response through RLR signaling pathway
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SVCV感染通过RLR信号通路触发鱼类IFN反应
DOI：
10.1016/j.fsi.2018.12.063
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发表时间：
2019-03-01
影响因子：
4.7
通讯作者：
Zhang, Yi-Bing
中科院分区：
文献类型：
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作者：
Gong, Xiu-Ying;Zhang, Qi-Min;Zhang, Yi-Bing
在哺乳动物中，病毒感染宿主细胞触发先天免疫应答，其特征在于诱导干扰素（IFN）和下游IFN刺激基因（ISG）。IFN抗病毒应答的启动依赖于宿主对病毒感染的识别。在鱼类中，类似的IFN抗病毒反应是诱导响应RNA或DNA病毒感染;然而，详细的机制识别给定的病毒和激活下游信号仍然在很大程度上未被探索。利用鲤鱼丘疹上皮瘤（Epithelioma papulosum cyprini，EPC）细胞和鲤鱼春季病毒血症病毒（Spring viremia of carp virus，SVCV）感染模型，研究了鱼类RLR信号通路参与SVCV诱导的鱼类IFN应答。IFN反应显着启动EPC细胞感染SVCV时，证明激活鱼IFN启动子，上调IFN和ISGs在mRNA和蛋白水平。然而，鱼类RLR家族的两种胞浆受体RIG-I和MDA 5的功能阻断显着减弱了鱼类IFN启动子的激活以及SVCV感染对鱼类IFN和ISG的诱导。与此同时，SVCV感染触发的IFN反应在EPC细胞中被阻断，当转染关键RLR信号传导因子的显性阴性突变体时，包括MAVS，MITA，TBK 1，IRF 3和IRF 7。这些结果共同揭示了保护的TLR介导的IFN信号，有助于鱼细胞响应RNA病毒感染。
In mammals, virus infection of host cells triggers innate immune response, characterized by induction of interferon (IFN) and downstream IFN-stimulated genes (ISGs). The initiation of IFN antiviral response is dependent on host recognition of virus infection. In fish, similar IFN antiviral response is induced in response to RNA or DNA virus infection; however, the detailed mechanisms underlying recognition of a given virus and activation of downstream signaling remain largely unexplored. Using an infection model with Epithelioma papulosum cyprini (EPC) cells and spring viremia of carp virus (SVCV), a negative sense single-stranded RNA virus, we reported that fish RLR signaling pathway was involved in SVCV-triggered fish IFN response. IFN response was significantly initiated in EPC cells when infected with SVCV, as evidenced by activation of fish IFN promoters, upregulation of IFN and ISGs at mRNA and protein levels. However, function blockade of RIG-I and MDA5, two cytosolic receptors of fish RLR family, significantly attenuated the activation of fish IFN promoters and also the induction of fish IFN and ISGs by SVCV infection. Consistently, SVCV infection-triggered IFN response were blocked in EPC cells when transfected with the dominant negative mutants of pivotal RLR signaling factors, including MAVS, MITA, TBK1, IRF3 and IRF7. These results together shed light on the conservation of RLR-mediated IFN signaling that contributes to fish cells responding to RNA virus infection.