A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells
A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells
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DOI：
10.1016/j.chom.2018.04.015
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发表时间：
2018-06-13
影响因子：
30.3
通讯作者：
Ohba, Yusuke
中科院分区：
文献类型：
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作者：
Fujioka, Yoichiro;Nishide, Shinya;Ohba, Yusuke
甲型流感病毒（IAV）感染是通过病毒糖蛋白血凝素（HA）与宿主细胞表面的唾液酸结合而引发的。然而，对IAV感染至关重要的含唾液酸的受体仍然未被鉴定。在这里，我们表明，HA结合电压依赖性Ca 2+通道Ca（v）1.2触发细胞内Ca 2+振荡和随后的IAV进入和复制。IAV进入被Ca 2+通道阻断剂（CCBs）或通过敲低Ca（v）1.2抑制。CCB地尔硫卓还可以抑制体内病毒复制。重新引入野生型但非糖基化缺陷的Ca（v）1.2突变体恢复了Cav1.2耗尽细胞中的Ca 2+振荡和病毒感染，证明了Ca（v）1.2唾液酸化的重要性。综上所述，我们确定Ca（v）1.2作为唾液酸化的宿主细胞表面受体，其结合HA并且对于IAV进入至关重要。
Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca2+ channel Ca(v)1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Ca(v)1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Ca(v)1.2 restored Ca2+ oscillations and virus infection in Cav1.2-depleted cells, demonstrating the significance of Ca(v)1.2 sialylation. Taken together, we identify Ca(v)1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.