Influenza A Viruses Enter Host Cells via Extracellular Ca Influx-Involved Clathrin-Mediated Endocytosis.

Influenza A virus (IAV) is internalized into its host cells by endocytosis, which involves many cellular proteins and molecules. In this study, we focus on the function of calcium ion (Ca) in IAV endocytosis. We have found that IAV infection is accompanied by the increase in concentration of cytosolic Ca, which is mainly attributed to the influx of extracellular Ca. When Ca influx is abolished, IAV internalization will be markedly suppressed, but the virus attachment to its host cells will be unaffected. Extracellular Ca influx is essential to the clathrin-mediated endocytosis (CME) of IAVs but dispensable to the clathrin-independent endocytosis of the virus and is dispensable to the CME of transferrin or low-density lipoprotein as a control. Ca influx might participate in the dynamin-promoted membrane fission in the CME of IAVs. Our study highlights that IAVs enter host cells via extracellular Ca influx-involved clathrin- and dynamin-dependent endocytosis, which will facilitate better understanding of IAV infection and development of anti-influenza drugs.