Zebrafish NF-κB/p65 Is Required for Antiviral Responses
Zebrafish NF-κB/p65 Is Required for Antiviral Responses
复制标题
斑马鱼 NF-κB/p65 是抗病毒反应所必需的。
DOI：
10.4049/jimmunol.1900309
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发表时间：
2020-06-01
影响因子：
4.4
通讯作者：
Xiao, Wuhan
中科院分区：
文献类型：
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作者：
Ouyang, Gang;Liao, Qian;Xiao, Wuhan
由NF-κ B家族调节的转录程序对于炎症反应以及先天性和适应性免疫是必不可少的。NF-κ B的激活通过两个主要的信号通路发生：经典和非经典。经典的NF-κ B通路响应于不同的免疫刺激，并导致快速但短暂的激活。p65作为典型的NF-κ B B家族的成员，被认为是病毒感染的关键调节因子。由于p65基因敲除小鼠的胚胎致死性，p65在抗病毒免疫应答中的生理作用仍不清楚。在这项研究中，我们产生了p65-null斑马鱼，这是可行的，在正常条件下，从他们的野生型（WT）的兄弟姐妹无法区分。然而，p65基因缺失的斑马鱼对鲤鱼病毒感染的春季病毒血症比它们的WT同胞更敏感。进一步的分析表明，促炎和抗病毒基因，包括IFN，下调p65-null斑马鱼后，春季病毒血症鲤鱼病毒感染与他们的WT兄弟姐妹相比。因此，我们的研究结果表明，p65是抗病毒反应所必需的，不仅激活促炎基因，而且激活抗病毒基因（包括IFN）。
Transcriptional programs regulated by the NF-kappa B family are essential for the inflammatory response as well as for innate and adaptive immunity. NF-kappa B activation occurs via two major signaling pathways: the canonical and the noncanonical. The canonical NF-kappa B pathway responds to diverse immune stimulations and leads to rapid but transient activation. As a member of the canonical NF-kappa B family, p65 is thought to be a key regulator of viral infection. Because of the embryonic lethality of p65-null mice, the physiological role of p65 in the antiviral immune response is still unclear. In this study, we generated p65-null zebrafish, which were viable and indistinguishable from their wildtype (WT) siblings under normal conditions. However, p65-null zebrafish were more sensitive to spring viremia of carp virus infection than their WT siblings. Further assays indicated that proinflammatory and antiviral genes, including IFN, were downregulated in p65-null zebrafish after spring viremia of carp virus infection compared with their WT siblings. Our results thus suggested that p65 is required for the antiviral response, activating not only proinflammatory genes but also antiviral genes (including IFN).