1. The Kv1.3 ion channel acts as a host factor restricting viral entry
- Author
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Fang Sun, Wei Yi, Jing Yao, Bingzheng Shen, Chang Xie, Yuting Cheng, Juan Hu, Fangfang Li, Minjun Gao, Yange Lang, Zhijian Cao, Qiang Liu, Zhenglin Ji, Yingliang Wu, and Zhiqiang Xia
- Subjects
0301 basic medicine ,Endosome ,Endosomes ,Hepacivirus ,Dengue virus ,medicine.disease_cause ,Transfection ,complex mixtures ,Biochemistry ,Respirovirus Infections ,Sendai virus ,Dengue ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Viral entry ,Cellular ion homeostasis ,Chlorocebus aethiops ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Vero Cells ,Ion channel ,Host factor ,Mice, Knockout ,Kv1.3 Potassium Channel ,Chemistry ,Zika Virus Infection ,Ficusin ,Zika Virus ,Dengue Virus ,Hydrogen-Ion Concentration ,Virus Internalization ,Hepatitis C ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,HEK293 Cells ,Membrane protein ,Hepatic stellate cell ,030217 neurology & neurosurgery ,Biotechnology - Abstract
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-infected Ifnar1-/- 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.
- Published
- 2020