Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Science, Hokkaido University, Sapporo 060-0812, Japan.
Cell Host Microbe. 2018 Jun 13;23(6):809-818.e5. doi: 10.1016/j.chom.2018.04.015. Epub 2018 May 17.
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 Ca channel Ca1.2 to trigger intracellular Ca oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca channel blockers (CCBs) or by knockdown of Ca1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Ca1.2 restored Ca oscillations and virus infection in Ca1.2-depleted cells, demonstrating the significance of Ca1.2 sialylation. Taken together, we identify Ca1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
甲型流感病毒（IAV）感染是由病毒糖蛋白血凝素（HA）与宿主细胞表面唾液酸上的 sialic acid 结合引发的。然而，对于 IAV 感染至关重要的含 sialic acid 的受体仍然未被鉴定。在这里，我们表明 HA 与电压依赖性钙通道 Ca1.2 结合，引发细胞内 Ca 振荡，随后引发 IAV 进入和复制。Ca 通道阻滞剂（CCBs）或 Ca1.2 的敲低可抑制 IAV 进入。CCB 地尔硫卓也可抑制体内的病毒复制。野生型 Ca1.2 的重新引入但不是糖基化缺陷突变体可恢复 Ca1.2 耗尽细胞中的 Ca 振荡和病毒感染，表明 Ca1.2 的唾液酸化的重要性。总之，我们将 Ca1.2 鉴定为一种与 HA 结合并对 IAV 进入至关重要的唾液酸化的宿主细胞表面受体。
