Institute of Virology Muenster (IVM), Centre for Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität, Muenster, Germany.
Cell Microbiol. 2020 Feb;22(2):e13143. doi: 10.1111/cmi.13143. Epub 2019 Dec 8.
The innate immune system, in particular the type I interferon (IFN) response, is a powerful defence against virus infections. In turn, many if not all viruses have evolved various means to circumvent, resist, or counteract this host response to ensure efficient replication and propagation. Influenza viruses are no exception to this rule, and several viral proteins have been described to possess IFN-antagonistic functions. Although the viral nonstructural protein 1 appears to be a major antagonist in influenza A and B viruses (IAV and IBV), we have previously shown that a specific motif in the IAV polymerase proteins exerts an IFN-suppressive function very early in infection. The question remained whether a similar function would also exist in IBV polymerases. Here, we show that indeed a specific amino acid position (A523) of the PB1 protein in the IBV polymerase complex confers IFN-antagonistic properties. Mutation of this position leads to enhanced activation of the IFN-mediated signalling pathway after infection and subsequent reduction of virus titres. This indicates that inhibition of innate immune responses is a conserved activity shared by polymerase proteins of IAV and IBV.
先天免疫系统，特别是 I 型干扰素（IFN）反应，是抵抗病毒感染的强大防御机制。反过来，许多（如果不是全部）病毒已经进化出各种手段来规避、抵抗或抵消这种宿主反应，以确保有效的复制和传播。流感病毒也不例外，已经描述了几种病毒蛋白具有 IFN 拮抗功能。虽然病毒非结构蛋白 1 似乎是 A 型和 B 型流感病毒（IAV 和 IBV）中的主要拮抗剂，但我们之前已经表明，IAV 聚合酶蛋白中的一个特定基序在感染早期就发挥 IFN 抑制功能。问题仍然是 IBV 聚合酶中是否也存在类似的功能。在这里，我们表明，IBV 聚合酶复合物中的 PB1 蛋白的特定氨基酸位置（A523）确实赋予了 IFN 拮抗特性。该位置的突变导致感染后 IFN 介导的信号通路的激活增强，随后病毒滴度降低。这表明抑制先天免疫反应是 IAV 和 IBV 聚合酶蛋白共有的保守活性。
