A groundbreaking new microscopy technique is offering an unprecedented look at how influenza viruses infect human cells, revealing a surprising active role played by the cells themselves. Researchers at ETH Zürich and collaborating institutions have, for the first time, directly observed this process in real-time, discovering that cells don’t simply allow viruses in – they actively work to capture them [[1]]. This research, published today in *PNAS*, not only deepens our understanding of viral infection but also opens new avenues for developing more targeted antiviral therapies [[1]],[[2]].
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12/04/2025 08:00
How Flu Viruses Enter Our Cells
Researchers have, for the first time, directly observed how influenza viruses infect cells using a new high-resolution microscopy method.
The international team, led by ETH Zürich, discovered that cells actively encourage virus uptake.
This method could now help develop more targeted antiviral therapies.
Fever, body aches, and a runny nose – the flu returns with the winter season. The illness is triggered by influenza viruses that enter our bodies through droplets and infect cells. Understanding this process is crucial for developing effective treatments and preventative measures.
Scientists from Switzerland and Japan have now conducted a detailed examination of this virus. Using a microscopy method they developed, they were able to zoom in on the surface of human cells in a petri dish. This allowed the researchers to observe, with high resolution and in real-time, how influenza viruses penetrate a living cell.
Surprisingly, the researchers, led by Yohei Yamauchi, Professor of Molecular Medicine at ETH Zürich, found that cells aren’t passively invaded by the flu virus. Instead, they actively try to capture the virus. “The infection of our body cells is like a dance between the virus and the cell,” Yamauchi said.
Viruses Surf on the Cell Surface
Of course, body cells don’t benefit from a viral infection. They gain nothing from actively participating in the process. This dynamic interplay occurs because viruses hijack a common cellular uptake mechanism that is essential for cells. This mechanism is normally used to transport vital substances, such as hormones, cholesterol, or iron, into the cells.
Just as with these substances, influenza viruses must attach to molecules on the cell surface. The dynamics resemble surfing on the cell surface: the virus scans the surface, attaching here and there to a surface molecule until it finds an ideal entry point – one where many of these receptor molecules are clustered together, allowing for efficient uptake into the cell.
After the cell, via its receptors, recognizes that a virus has attached to its membrane, it forms a depression or pocket at that location. This is shaped and stabilized by special structural proteins called clathrin. Gradually, the invagination grows and encloses the virus, forming a vesicle. The cell transports this vesicle inside, where the vesicle shell dissolves and releases the virus.
Previous studies investigating this important process used other microscopy methods, including electron microscopy. These methods require destroying the cells, allowing only for snapshots in time. Another method used, fluorescence microscopy, only allows for low spatial resolution.
Combined Methods, Also for Other Viruses
The new method is a combination of atomic force and fluorescence microscopy. They call the method Virus-View Raster Force Microscopy. Vivid stands for “Virus View.” This technology made it possible to track the virus’s entry into the cell in all the details of its dynamics.
With this, the researchers were able to show that the cell actively promotes virus uptake at various stages. For example, the cell actively recruits the functionally important clathrin proteins to the location where the virus is located. Furthermore, the cell surface ripples at this point to actively capture the virus with the undulations. These wave-like membrane movements become stronger when the virus moves away from the cell surface.
The new method provides important insights for the development of antiviral drugs. For example, it is suitable for testing the effect of potential drugs in cell culture in real-time. As the study authors emphasize, the method can also be used to investigate the behavior of other viruses or vaccines.
Contact for scientific information:
Prof. Dr. Yohei Yamauchi
yohei.yamauchi@pharma.ethz.ch
Original publication:
Yoshida A, Uekusa Y, Suzuki T, Bauer M, Sakai N, Yamauchi Y: Enhanced visualization of influenza A virus entry into living cells using virus-view atomic force microscopy. PNAS, 122: e2500660122, doi: 10.1073/pnas.2500660122
More information:
https://ethz.ch/de/news-und-veranstaltungen/eth-news/news/2025/12/wie-grippevire…
://Youtube-Video: https://youtu.be/zySUz2kbbnA?si=ogo_tBu7xADQBBY5 (Credits: Nicole Davidson / ETH Zürich)
Images
Cells actively help capture and incorporate influenza viruses. Here is a cell and a virus in the center of the image. …
Source: Emma Hyde
Copyright: ETH Zürich
Criteria of this press release:
Journalists, Scientists and scholars
Biology, Information technology, Medicine
transregional, national
Research results, Transfer of Science or Research
German
