Influenza A virus (IAV) PA‐X is a critical ribonuclease protein involved in host cell shutoff but its role in modulating the host immune response to IAV infection remains to be addressed. In this study, host cellular proteins that directly interact with PA‐X were screened to investigate the biological function of PA‐X in the pathogenesis of IAV infection. The protein ankyrin repeat domain 17 (Ankrd17), a positive regulator of inflammatory responses via the retinoic acid‐inducible gene‐I (RIG‐I)‐like receptor (RLR) signaling pathway, was identified as a specific PA‐X binding partner that preferred PA‐X to the PA protein. The N‐terminal ankyrin repeats of Ankrd17 are the key domain for the interaction with PA‐X rather than PA, which is required for the function of Ankrd17 in elevating the host immune response. Using Ankrd17 knockout and overexpression, we confirmed that PA‐X significantly affected the Ankrd17‐mediated response to infection in host cells. Our data therefore reveal a novel function for PA‐X in the regulation of innate immune pathways via the interaction between PA‐X and Ankrd17.

中文翻译：

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甲型流感病毒蛋白 PA-X 抑制宿主 Ankrd17 介导的免疫反应

甲型流感病毒 (IAV) PA-X 是一种参与宿主细胞关闭的关键核糖核酸酶蛋白，但其在调节宿主对 IAV 感染的免疫反应中的作用仍有待解决。本研究筛选了与 PA-X 直接相互作用的宿主细胞蛋白，以研究 PA-X 在 IAV 感染发病机制中的生物学功能。蛋白锚蛋白重复结构域 17 (Ankrd17) 是通过视黄酸诱导基因 I (RIG-I) 样受体 (RLR) 信号通路对炎症反应的正调节因子，被鉴定为特定的 PA-X 结合伴侣与 PA 蛋白相比，PA-X 更受欢迎。Ankrd17 的 N 端锚蛋白重复序列​​是与 PA-X 相互作用的关键域，而不是 PA，这是 Ankrd17 提高宿主免疫反应功能所必需的。使用 Ankrd17 敲除和过表达，我们证实 PA-X 显着影响 Ankrd17 介导的宿主细胞感染反应。因此，我们的数据揭示了 PA-X 通过 PA-X 和 Ankrd17 之间的相互作用在调节先天免疫途径中的新功能。