tetano
Editor, Senior Moderator
Cell Host Microbe. 2018 May 10. pii: S1931-3128(18)30216-6. doi: 10.1016/j.chom.2018.04.015. [Epub ahead of print]
[h=1]A Sialylated Voltage-Dependent Ca[SUP]2+[/SUP] Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.[/h] Fujioka Y[SUP]1[/SUP], Nishide S[SUP]1[/SUP], Ose T[SUP]2[/SUP], Suzuki T[SUP]3[/SUP], Kato I[SUP]4[/SUP], Fukuhara H[SUP]4[/SUP], Fujioka M[SUP]1[/SUP], Horiuchi K[SUP]1[/SUP], Satoh AO[SUP]1[/SUP], Nepal P[SUP]1[/SUP], Kashiwagi S[SUP]1[/SUP], Wang J[SUP]1[/SUP], Horiguchi M[SUP]1[/SUP], Sato Y[SUP]3[/SUP], Paudel S[SUP]1[/SUP], Nanbo A[SUP]1[/SUP], Miyazaki T[SUP]5[/SUP], Hasegawa H[SUP]3[/SUP], Maenaka K[SUP]6[/SUP], Ohba Y[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]2+[/SUP] channel Ca[SUB]v[/SUB]1.2 to trigger intracellular Ca[SUP]2+[/SUP] oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca[SUP]2+[/SUP] channel blockers (CCBs) or by knockdown of Ca[SUB]v[/SUB]1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Ca[SUB]v[/SUB]1.2 restored Ca[SUP]2+[/SUP] oscillations and virus infection in Ca[SUB]v[/SUB]1.2-depleted cells, demonstrating the significance of Ca[SUB]v[/SUB]1.2 sialylation. Taken together, we identify Ca[SUB]v[/SUB]1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
[h=4]KEYWORDS:[/h] 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
[h=1]A Sialylated Voltage-Dependent Ca[SUP]2+[/SUP] Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.[/h] Fujioka Y[SUP]1[/SUP], Nishide S[SUP]1[/SUP], Ose T[SUP]2[/SUP], Suzuki T[SUP]3[/SUP], Kato I[SUP]4[/SUP], Fukuhara H[SUP]4[/SUP], Fujioka M[SUP]1[/SUP], Horiuchi K[SUP]1[/SUP], Satoh AO[SUP]1[/SUP], Nepal P[SUP]1[/SUP], Kashiwagi S[SUP]1[/SUP], Wang J[SUP]1[/SUP], Horiguchi M[SUP]1[/SUP], Sato Y[SUP]3[/SUP], Paudel S[SUP]1[/SUP], Nanbo A[SUP]1[/SUP], Miyazaki T[SUP]5[/SUP], Hasegawa H[SUP]3[/SUP], Maenaka K[SUP]6[/SUP], Ohba Y[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]2+[/SUP] channel Ca[SUB]v[/SUB]1.2 to trigger intracellular Ca[SUP]2+[/SUP] oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca[SUP]2+[/SUP] channel blockers (CCBs) or by knockdown of Ca[SUB]v[/SUB]1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Ca[SUB]v[/SUB]1.2 restored Ca[SUP]2+[/SUP] oscillations and virus infection in Ca[SUB]v[/SUB]1.2-depleted cells, demonstrating the significance of Ca[SUB]v[/SUB]1.2 sialylation. Taken together, we identify Ca[SUB]v[/SUB]1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
[h=4]KEYWORDS:[/h] 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