The Kv1.3 ion channel acts as a host factor restricting viral entry

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.

Automated summary

The functional Kv1.3 ion channel restricts the entry of HCV, DENV, and ZIKV by inhibiting endosome acidification-mediated viral membrane fusion, with no effect on SeV. The Kv1.3 antagonist PAP-1 accelerates animal death in ZIKV-infected Ifnar1(-/-) mice, and deletion of Kv1.3 promotes weight loss and reduces survival rate in ZIKV-infected Kv1.3(-/-) mice. Overall, the Kv1.3 ion channel acts as a host factor that limits viral entry and expands understanding of ion channel biology.