College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China.
Viruses. 2020 Mar 12;12(3):307. doi: 10.3390/v12030307.
MDA5 belongs to the RIG-I-like receptor family, which is involved in innate immunity. During viral infection, MDA5 generates an antiviral response by recognizing the ligand to activate interferon. However, the role and mechanism of MDA5 in canine influenza virus (CIV) infection are unclear. To understand the mechanism of canine MDA5-mediated innate immunity during CIV infection, we detected the distribution of MDA5 in beagles, and the structural prediction showed that MDA5 was mainly composed of a CARD domain, RD domain, and DExD/H helix structure. Moreover, we found that MDA5 inhibits CIV replication. Furthermore, in the dual luciferase assay, we revealed that the CARD region of MDA5 strongly activated the IFN-β promoter and mainly transmitted signals through the CARD region. Overexpression of the CARD region of MDA5 revealed that the MDA5-mediated signaling pathway could transmit signals by activating the IRF3/NF-κB and IRF3 promoters, promoting the expression of antiviral proteins and cytokine release, thereby inhibiting CIV replication. Upon silencing of MDA5, cytokine production decreased, while the replication ability of CIV was increased. Thus, this study revealed a novel mechanism by which MDA5 mediated CIV infection and provided new avenues for the development of antiviral strategies.
MDA5 属于 RIG-I 样受体家族，参与先天免疫。在病毒感染过程中，MDA5 通过识别配体激活干扰素产生抗病毒反应。然而，MDA5 在犬流感病毒（CIV）感染中的作用和机制尚不清楚。为了了解 MDA5 介导的犬科先天免疫在 CIV 感染中的机制，我们检测了 MDA5 在比格犬中的分布，结构预测表明 MDA5 主要由 CARD 结构域、RD 结构域和 DExD/H 螺旋结构组成。此外，我们发现 MDA5 抑制 CIV 复制。此外，在双荧光素酶测定中，我们揭示 MDA5 的 CARD 区域强烈激活 IFN-β 启动子，主要通过 CARD 区域传递信号。MDA5 的 CARD 区域的过表达表明，MDA5 介导的信号通路可以通过激活 IRF3/NF-κB 和 IRF3 启动子来传递信号，促进抗病毒蛋白和细胞因子的释放，从而抑制 CIV 复制。沉默 MDA5 后，细胞因子的产生减少，而 CIV 的复制能力增加。因此，本研究揭示了 MDA5 介导 CIV 感染的新机制，为抗病毒策略的发展提供了新途径。
