The Kv1.3 ion channel acts as a host factor restricting viral entry.
The Kv1.3 ion channel acts as a host factor restricting viral entry.
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Kv1.3离子通道充当限制病毒进入的宿主因子
DOI：
10.1096/fj.202000879rr
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Cao Zhijian
中科院分区：
文献类型：
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作者：
Lang Yange;Li Fangfang;Liu Qiang;Xia Zhiqiang;Ji Zhenglin;Hu Juan;Cheng Yuting;Gao Minjun;Sun Fang;Shen Bingzheng;Xie Chang;Yi Wei;Wu Yingliang;Yao Jing;Cao Zhijian
病毒进入细胞是感染的初始阶段，涉及多个步骤，干扰病毒进入代表了潜在的抗病毒方法。离子通道是控制细胞离子稳态和调节许多生理过程的成孔膜蛋白，但它们在病毒感染期间的作用很少被探索。在此，发现功能性Kv1.3离子通道在人肝细胞和组织中表达。然后发现Kv1.3通过抑制内体酸化介导的病毒膜融合来限制HCV进入。Kv1.3也被证明抑制DENV和ZIKV，具有内体酸化依赖性进入，但对SeV没有影响，具有中性pH渗透。Kv1.3拮抗剂PAP-1治疗加速了ZIKV感染的Ifnar 1 −/−小鼠的动物死亡。此外，发现Kv1.3-缺失促进ZIKV感染的Kv1.3−/−小鼠的体重减轻并降低存活率。总之，Kv1.3离子通道作为限制病毒进入的宿主因子。这些发现拓宽了对离子通道生物学的理解。
Virus entry into cells is the initial stage of infection and involves multiple steps, and interfering viral entry represents potential antiviral approaches. Ion channels are pore‐forming membrane proteins controlling cellular ion homeostasis and regulating many physiological processes, but their roles during viral infection have rarely been explored. Here, the functional Kv1.3 ion channel was found to be expressed in human hepatic cells and tissues. The Kv1.3 was then revealed to restrict HCV entry via inhibiting endosome acidification‐mediated viral membrane fusion. The Kv1.3 was also demonstrated to inhibit DENV and ZIKV with an endosome acidification‐dependent entry, but have no effect on SeV with a neutral pH penetration. A Kv1.3 antagonist PAP‐1 treatment accelerated animal death in ZIKV‐infectedIfnar1−/−mice. Moreover, Kv1.3‐deletion was found to promote weight loss and reduce survival rate in ZIKV‐infected Kv1.3−/−mice. Altogether, the Kv1.3 ion channel behaves as a host factor restricting viral entry. These findings broaden understanding about ion channel biology.