School of Life Science, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China.
Virus Genes. 2023 Apr;59(2):215-222. doi: 10.1007/s11262-022-01958-w. Epub 2022 Nov 21.
The host innate immune response to viral infection often involves the activation of type I interferons. Not surprisingly, many viruses have evolved various mechanisms to disable the interferon pathway and evade the antiviral response involving innate immunity. Rabbit hemorrhagic disease (RHD) is caused by RHD virus (RHDV), but whether it can antagonize the production of host interferon to establish infection has not been investigated. In this study, we found that during RHDV infection, the expressions of interferon and the interferon-stimulated gene were not activated. We constructed eukaryotic expression plasmids of all RHDV proteins, and found that RHDV 3C protein inhibited poly(I:C)-induced interferon expressions. Using siRNA to interfere with the expressions of TLR3 and MDA5, we found that the MDA5 signal pathway was used by the 3C protein to inhibit poly(I:C)-induced interferon expression. This effect was mediated by cleaving the interferon promoter stimulated 1 (IPS-1) protein. Finally, our study showed that interferon was effective against RHDV infection. In summary, our findings showed that the RHDV 3C protein was a new interferon antagonist. These results increase our understanding of the escape mechanism from innate immunity mediated by the RHDV 3C protein.
宿主对病毒感染的固有免疫反应通常涉及 I 型干扰素的激活。毫不奇怪，许多病毒已经进化出各种机制来破坏干扰素途径，从而逃避涉及固有免疫的抗病毒反应。兔出血症（RHD）由兔出血症病毒（RHDV）引起，但它是否能拮抗宿主干扰素的产生以建立感染尚未被研究。在这项研究中，我们发现 RHDV 感染期间，干扰素和干扰素刺激基因的表达未被激活。我们构建了所有 RHDV 蛋白的真核表达质粒，并发现 RHDV 3C 蛋白抑制聚（I:C）诱导的干扰素表达。使用 siRNA 干扰 TLR3 和 MDA5 的表达，我们发现 3C 蛋白利用 MDA5 信号通路抑制聚（I:C）诱导的干扰素表达。这种作用是通过切割干扰素启动子刺激 1（IPS-1）蛋白介导的。最后，我们的研究表明干扰素对 RHDV 感染有效。总之，我们的研究结果表明，RHDV 3C 蛋白是一种新的干扰素拮抗剂。这些结果增加了我们对 RHDV 3C 蛋白介导的固有免疫逃避机制的理解。
