State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
The Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan 430072, China.
J Immunol. 2020 Jun 1;204(11):3019-3029. doi: 10.4049/jimmunol.1900309. Epub 2020 Apr 22.
Transcriptional programs regulated by the NF-κB family are essential for the inflammatory response as well as for innate and adaptive immunity. NF-κB activation occurs via two major signaling pathways: the canonical and the noncanonical. The canonical NF-κB pathway responds to diverse immune stimulations and leads to rapid but transient activation. As a member of the canonical NF-κB 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).
NF-κB 家族调控的转录程序对于炎症反应以及先天和适应性免疫至关重要。NF-κB 的激活通过两条主要信号通路发生：经典途径和非经典途径。经典的 NF-κB 途径对各种免疫刺激做出反应，导致快速但短暂的激活。作为经典 NF-κB 家族的一员，p65 被认为是病毒感染的关键调节因子。由于 p65 基因敲除小鼠具有胚胎致死性，因此 p65 在抗病毒免疫反应中的生理作用仍不清楚。在这项研究中，我们生成了 p65 基因敲除斑马鱼，它们在正常条件下与野生型（WT）同窝仔鱼一样存活且无法区分。然而，p65 基因敲除斑马鱼在 Spring Viremia of Carp Virus（SVCV）感染后比 WT 同窝仔鱼更敏感。进一步的检测表明，在 SVCV 感染后，与 WT 同窝仔鱼相比，促炎和抗病毒基因（包括 IFN）在 p65 基因敲除斑马鱼中下调。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，还激活抗病毒基因（包括 IFN）。
