Study Finds Changes in Ca2+ Concentration in Host Cells Play a Key Role in IAV Infection

Copyright © iCell Bioscience Inc, Shanghai 2018-2019

After more than 10 years of research, a research team finally discovered key receptor molecules that enhance the infection of influenza A virus, providing new targets for the development of new influenza A virus drugs.

When the virus particle adheres to the host cell surface molecule, this cell begins to be infected. Virus particles then hijack the cellular components into the cell and replicate, causing infection. Despite studying for more than ten years, the receptor molecules to which Influenza A virus (IAV) binds have not yet been discovered.

A team led by Prof. Yusuke Ohba of Hokkaido University found that changes in Ca2+ concentration in host cells play a key role in IAV infection.

In the latest study published in Cell Host & Microbe, the team found that calcium channel proteins (a transmembrane protein that allows calcium ions to pass through cell membranes into cells) are key receptors for IAV infection. Researchers further treated human cells with calcium channel inhibitors (CCBs, a commonly used antihypertensive drug) to significantly reduce IAV infection.

In tests on cultured human cells, the researchers found that IAV binds calcium channel proteins and produces a flow of calcium ions into the cells. The virus then enters the cells and causes infection. Knockout of calcium channel protein can inhibit IAV-induced calcium flow and viral infection. They also found that sialic acid on calcium channel proteins is the key point for virus binding.

Finally, the researchers tested the effects of CCB on IAV infection in mice. When they administered CCB intranasally to mice, it was observed that the number of viral replications exhibited a significant dose-dependent decrease. When mice were exposed to large amounts of IAV, the injection of CCB significantly prolonged the survival time of the mice and prompted recovery of body weight in the survivors, whereas the mice in the control group all died within five days.

The researchers found that the effect of CCB in inhibiting IAV was comparable to that of some existing anti-influenza drugs. It is hoped that the interaction between IAV and calcium channel proteins can provide important new targets for drug development.