Li Ning, Zhang Yanxu, Wu Shuangxiu, Xu Ruodan, Li Zhiqing, Zhu Jindong, Wang Hongliang, Li Xiao, Tian Mingyao, Lu Huijun, Jin Ningyi, Jiang Chengyu
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
Interdisciplinary Nanoscience Center (iNANO), Department of Engineering, Aarhus University, 8000 Aarhus C, Denmark.
Sci Bull (Beijing). 2019 Feb 15;64(3):180-188. doi: 10.1016/j.scib.2018.08.013. Epub 2018 Sep 1.
Influenza is a persistent threat to human health and there is a continuing requirement for updating anti-influenza strategies. Initiated by observations of different endoplasmic reticulum (ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza (HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid (TUDCA), a clinically available ER stress inhibitor, both and . Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity, an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.
流感对人类健康构成持续威胁，因此不断需要更新抗流感策略。基于对宿主对季节性H1N1和高致病性禽流感（HPAI）A H5N1感染的不同内质网（ER）反应的观察，我们确定了牛磺熊去氧胆酸（TUDCA）（一种临床上可用的ER应激抑制剂）在体内和体外的另一种抗病毒作用。TUDCA不是调节宿主细胞中的ER应激，而是通过破坏病毒M2的寡聚状态来消除其质子传导性，从而导致病毒感染效率低下。我们还表明，M2进入细胞，其细胞内摄取取决于其质子通道活性，在TUDCA和M2抑制剂金刚烷胺中均观察到这种效应。TUDCA作为M2质子通道抑制剂的鉴定和应用将扩展我们对甲型流感病毒生物学的理解，并补充当前的抗甲型流感病毒手段。
