Key flu target identified

A key cell receptor that facilitates influenza A virus infection has been identified following decades of research.

Human bronchial epithelial cells cultured without (left) and with (right) a calcium channel blocker prior to exposure to influenza A virus (IAV). Red signals show infected and replicated IAV in the left panel. Treatment with calcium channel blockers significantly suppressed IAV infection as seen in the right panel.

Viral infection starts when a virus particle attaches to a receptor on the surface of a host cell. The virus particle then hijacks cellular machinery to enter the cell and replicate, establishing the infection. The key receptor for the influenza A virus (IAV) has remained unidentified despite decades of research.

A team led by Yusuke Ohba of Hokkaido University found that the calcium ion (Ca2+) channel – a transmembrane protein that allows Ca2+ to move across the cell membrane – is the key receptor for IAV infections. Treating human cells with calcium channel blockers, commonly used to treat hypertension, significantly suppressed IAV infections.

The findings build on the group’s previous research demonstrating that changes in calcium ion concentration in host cells play an important role in IAV infections.

The team found, using cultured human cells, that IAV binds to a calcium channel on a cell’s surface to trigger an influx of Ca2+. This is followed by virus entry and infection. Turning off calcium channel activity prevented IAV-induced Ca2+ influx and virus entry. The team found that the presence of sialic acid on the Ca2+ channel is crucial for virus binding.

The researchers treated mice with calcium channel blockers through the nose before or after IAV infection. This led to a significant and dose-dependent reduction in the numbers of replicated viruses within cells. Mice infected with large numbers of IAV survived much longer and had better weight recovery following administration of calcium channel blockers compared to an untreated group, which died within five days.

“We expect that the interaction between IAV and the Ca2+ channel could be a novel and important target for future drug development,” says Ohba.

The study was published in the journal Cell Host & Microbe.

For further information, contact:

Professor Yusuke Ohba
Department of Cell Physiology
Hokkaido University
E-mail: [email protected]