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Cell Host Microbe. 2018 May 10. pii: S1931-3128(18)30216-6. doi: 10.1016/j.chom.2018.04.015. [Epub ahead of print]
A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.
Fujioka Y1, Nishide S1, Ose T2, Suzuki T3, Kato I4, Fukuhara H4, Fujioka M1, Horiuchi K1, Satoh AO1, Nepal P1, Kashiwagi S1, Wang J1, Horiguchi M1, Sato Y3, Paudel S1, Nanbo A1, Miyazaki T5, Hasegawa H3, Maenaka K6, Ohba Y7.
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Abstract
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 Cav1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Cav1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Cav1.2 restored Ca2+ oscillations and virus infection in Cav1.2-depleted cells, demonstrating the significance of Cav1.2 sialylation. Taken together, we identify Cav1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
KEYWORDS:
calcium channel; calcium channel blockers; calcium ion; hemagglutinin; influenza A virus; sialylation; virus entry; virus-host cell interaction
PMID: 29779930 DOI: 10.1016/j.chom.2018.04.015
A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.
Fujioka Y1, Nishide S1, Ose T2, Suzuki T3, Kato I4, Fukuhara H4, Fujioka M1, Horiuchi K1, Satoh AO1, Nepal P1, Kashiwagi S1, Wang J1, Horiguchi M1, Sato Y3, Paudel S1, Nanbo A1, Miyazaki T5, Hasegawa H3, Maenaka K6, Ohba Y7.
Author information
Abstract
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 Cav1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Cav1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Cav1.2 restored Ca2+ oscillations and virus infection in Cav1.2-depleted cells, demonstrating the significance of Cav1.2 sialylation. Taken together, we identify Cav1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
KEYWORDS:
calcium channel; calcium channel blockers; calcium ion; hemagglutinin; influenza A virus; sialylation; virus entry; virus-host cell interaction
PMID: 29779930 DOI: 10.1016/j.chom.2018.04.015