Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of Cell Press for personal use, not for redistribution. The definitive version was published in Cell Host and Microbe 23 (2018): 809-818, doi:10.1016/j.chom.2018.04.015.
Description:
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.
Description:
This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan
(#26115701 and #15H01248), from the Japan Society for the Promotion of Science
(#26293041 and #16H06227), and from the Japan Agency for Medical Research and
Development (JP17fk0108124j0601), as well as by grants from Mochida Memorial
Foundation for Medical and Pharmaceutical Research, the Waksman Foundation of Japan, the
Sumitomo Electric Group Corporate Social Responsibility Foundation, and SENSHIN
Medical Research Foundation.
Description:
2019-05-17
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Permalink
