Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
Sci Rep. 2019 May 10;9(1):7216. doi: 10.1038/s41598-019-43632-6.
The sensing of viral nucleic acids by the innate immune system activates a potent antiviral response in the infected cell, a key component of which is the expression of genes encoding type I interferons (IFNs). Many viruses counteract this response by blocking the activation of host nucleic acid sensors. The evolutionarily conserved influenza A virus (IAV) protein PA-X has been implicated in suppressing the host response to infection, including the expression of type I IFNs. Here, we characterise this further using a PA-X-deficient virus of the mouse-adapted PR8 strain to study activation of the innate immune response in a mouse model of the early response to viral infection. We show that levels of Ifna4 and Ifnb1 mRNAs in the lungs of infected mice were elevated in the absence of PA-X and that this was completely dependent on MAVS. This therefore suggests a role for PA-X in preventing the accumulation of early type I IFN mRNAs in the lung during IAV infection.
先天免疫系统对病毒核酸的感应激活了受感染细胞中的强烈抗病毒反应，其中的一个关键组成部分是编码 I 型干扰素 (IFN) 的基因的表达。许多病毒通过阻止宿主核酸传感器的激活来对抗这种反应。已发现进化上保守的甲型流感病毒 (IAV) 蛋白 PA-X 参与抑制宿主对感染的反应，包括 I 型 IFN 的表达。在这里，我们使用缺乏 PA-X 的小鼠适应 PR8 株的病毒进一步对此进行了描述，以研究在病毒感染早期的小鼠模型中先天免疫反应的激活。我们发现，在缺乏 PA-X 的情况下，感染小鼠肺部的 Ifna4 和 Ifnb1 mRNA 水平升高，而这完全依赖于 MAVS。因此，这表明 PA-X 在防止 IAV 感染期间肺中早期 I 型 IFN mRNA 的积累中起作用。
