An international team led by ETH Zurich and including researchers in Japan has used a new high‑resolution imaging technique to watch, live, as influenza viruses penetrate human cells. The work shows that cells actively engage with the virus, helping to draw it inside in a process that resembles surfing along the cell membrane, and could inform the development of targeted antiviral therapies.
Influenza viruses cause seasonal illness marked by fever, aching limbs and runny noses, entering the body via droplets and then infecting cells in the airways, ETH Zurich reports.
Researchers from Switzerland and Japan have now examined this infection process in unprecedented detail. Using a microscopy technique they developed themselves, the team can zoom in on the surface of human cells growing in a Petri dish and observe, live and in high resolution, how individual influenza A viruses enter living cells.
The study, led by Yohei Yamauchi, Professor of Molecular Medicine at ETH Zurich, found that cells are not passive victims. Instead, they actively contribute to the virus’s uptake. “The infection of our body cells is like a dance between virus and cell,” Yamauchi said.
Although the cells gain nothing from being infected, the virus hijacks a routine cellular uptake system that the cells rely on to import essential substances such as hormones, cholesterol and iron.
To begin infection, an influenza virus binds to specific molecules on the cell surface. According to ETH Zurich, the virus then effectively ‘surfs’ along the membrane, attaching to successive molecules and scanning the surface until it reaches an entry site where many receptor molecules are clustered together, enabling efficient uptake.
Once the cell’s receptors detect that a virus has attached to the membrane, the cell begins to wrap itself around the particle. A small indentation, or pocket, forms at that spot and is shaped and stabilised by the structural protein clathrin. As the pocket deepens, it encloses the virus and buds off as a vesicle. The cell transports this vesicle into its interior, where the vesicle’s coat dissolves and releases the virus.
Using the new technique, the researchers showed that cells assist the virus at several stages of this process. They actively recruit clathrin proteins to the site where the virus is bound, and the cell surface bulges upwards to help capture the particle. These wave‑like membrane movements intensify if the virus starts to drift away from the surface.
Until now, key aspects of influenza entry had been studied mainly with electron microscopy, which requires cells to be fixed and destroyed and therefore only provides static snapshots, or with fluorescence microscopy, which offers lower spatial resolution and limited insight into nanoscale surface dynamics.
The new approach, called virus‑view dual confocal and AFM (ViViD‑AFM), combines atomic force microscopy with fluorescence microscopy to follow the fine‑scale dynamics of virus entry in real time. The method is described in detail in a paper titled Enhanced visualization of influenza A virus entry into living cells using virus‑view atomic force microscopy, published in the Proceedings of the National Academy of Sciences in September 2025.
Because ViViD‑AFM allows scientists to watch infection as it happens, the ETH Zurich team says it provides a powerful way to test antiviral drug candidates directly in cell cultures under realistic conditions. The researchers also note that the technique could be applied to study other viruses or even vaccines, offering real‑time views of how diverse particles interact with and are taken up by cells.
