Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma, Stillwater, USA.
Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Oklahoma, Stillwater, USA.
Mol Microbiol. 2022 Dec;118(6):731-743. doi: 10.1111/mmi.14995. Epub 2022 Nov 5.
Acute respiratory infection by influenza virus is a persistent and pervasive public health problem. Antiviral innate immunity initiated by type I interferon (IFN) is the first responder to pathogen invasion and provides the first line of defense. We discovered that Axin1, a scaffold protein, was reduced during influenza virus infection. We also found that overexpression of Axin1 and the chemical stabilizer of Axin1, XAV939, reduced influenza virus replication in lung epithelial cells. This effect was also observed with respiratory syncytial virus and vesicular stomatitis virus. Axin1 boosted type I IFN response to influenza virus infection and activated JNK/c-Jun and Smad3 signaling. XAV939 protected mice from influenza virus infection. Thus, our studies provide new mechanistic insights into the regulation of the type I IFN response and present a new potential therapeutic of targeting Axin1 against influenza virus infection.
流感病毒引起的急性呼吸道感染是一个持续存在的普遍公共卫生问题。Ⅰ型干扰素（IFN）介导的抗病毒固有免疫是对病原体入侵的第一反应，提供第一道防线。我们发现，在流感病毒感染过程中支架蛋白 Axin1 减少。我们还发现，Axin1 的过表达和 Axin1 的化学稳定剂 XAV939 可降低肺上皮细胞中的流感病毒复制。呼吸道合胞病毒和水疱性口炎病毒也观察到了这种效应。Axin1 增强了Ⅰ型 IFN 对流感病毒感染的反应，并激活了 JNK/c-Jun 和 Smad3 信号通路。XAV939 可保护小鼠免受流感病毒感染。因此，我们的研究为Ⅰ型 IFN 反应的调节提供了新的机制见解，并提出了一种针对流感病毒感染靶向 Axin1 的新的潜在治疗方法。
