Tauroursodeoxycholic acid (TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2
Tauroursodeoxycholic acid (TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2
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牛磺熊去氧胆酸 (TUDCA) 通过破坏病毒质子通道 M2 抑制甲型流感病毒感染
DOI：
10.1016/j.scib.2018.08.013
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发表时间：
2019-02-15
期刊：
影响因子：
18.9
通讯作者：
Jiang, Chengyu
中科院分区：
文献类型：
--
作者：
Li, Ning;Zhang, Yanxu;Jiang, Chengyu
流感是对人类健康的持续威胁，需要不断更新抗流感战略。从观察宿主对季节性H1N1和高致病性禽流感(HPAI)H5N1感染的不同内质网(ER)反应开始，我们在体外和体内确定了临床上可用的ER应激抑制剂牛磺酸脱氧胆酸(TUDCA)的另一种抗病毒作用。TUDCA没有调节宿主细胞中的内质网应激，而是通过破坏病毒M2的寡聚体状态来取消病毒M2的质子传导性，从而导致低效病毒感染。我们还发现M2能穿透细胞，细胞内的摄取依赖于它的质子通道活性，这一效应在TUDCA和M2抑制剂金刚烷胺中都观察到了。TUDCA作为M2质子通道抑制剂的发现和应用，将扩大我们对IAV生物学的认识，补充现有的抗IAV药物。(三)2018年科学中国出版社。爱思唯尔出版社、科学中国出版社出版。版权所有。
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 in vitro and in vivo. 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. (C) 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.