ETH Zurich microscopy method identifies how influenza viruses infect cells

08 Dec 2025

Combined AFM and fluorescence approach enables live and high-resolution imaging.

Cells actively help to capture and incorporate influenza viruses.

For the first time, researchers have observed live and in high resolution how influenza (“flu”) viruses infect living cells. This was possible thanks to a new microscopy technique, developed at ETH Zurich, Switzerland, which could now help to develop antiviral therapies in a more targeted manner.

Flu is triggered by influenza viruses, which enter the human body through droplets and then infect cells. A combined team from Switzerland and Japan have been investigating this virus in minute detail.

Using a microscopy technique that they developed themselves, the scientists can zoom in on the surface of human cells in a Petri dish. For the first time, this has allowed them to observe live and in high resolution how influenza viruses enter a living cell.

Led by Yohei Yamauchi, Professor of Molecular Medicine at ETH Zurich, the researchers were surprised by one thing in particular: the cells are not passive, simply allowing themselves to be invaded by the influenza virus. Rather, they actively attempt to capture it. “The infection of our body cells is like a dance between virus and cell,” said Yamauchi.

The work is described in a paper in PNAS (Proceedings of the National Academy of Sciences, USA).

Viruses surf on the cell surface

The dynamic interplay takes place because the viruses commandeer an everyday cellular uptake mechanism that is essential for the cells. Specifically, this mechanism serves to channel vital substances, such as hormones, cholesterol or iron, into the cells.

Like these substances, influenza viruses must also attach to molecules on the cell surface. The researchers say that the process dynamics are “like surfing on the surface of the cell; the virus scans the surface, attaching to a molecule, until it has found an ideal entry point, enabling efficient uptake into the cell”.

Once the cell’s receptors detect that a virus has attached itself to the membrane, a depression or pocket forms at the location in question. This depression is shaped and stabilised by a special structural protein known as clathrin. As the pocket grows, it encloses the virus, leading to the formation of a vesicle. The cell transports this vesicle into its interior, where the vesicle coating dissolves and releases the virus.

Combined techniques

Previous studies investigating this key process used other microscopy techniques, including electron microscopy. As these techniques entailed the destruction of the cells, they could only ever provide a snapshot. Another technique that is used – known as fluorescence microscopy – only allows low spatial resolution.

The new technique, which combines atomic force microscopy (AFM) and fluorescence microscopy, is known as virus-view dual confocal and AFM (ViViD-AFM). Thanks to this method, say the researchers, it is now possible to follow the detailed dynamics of the virus’s entry into the cell. Accordingly, the researchers have been able to show that the cell actively promotes virus uptake on various levels.

The new technique therefore provides key insights when it comes to the development of antiviral drugs. For example, it is suitable for testing the efficacy of potential drugs in a cell culture in real time. The study authors emphasise that the technique could also be used to investigate the behaviour of other viruses or even vaccines.