Breakthrough Study Shows How Influenza A Hijacks Human Cells

For the first time, a team of researchers has drawn a detailed picture of how influenza A snatches control of the very cells it infects. By peeking inside living human cells, they were able to chart dozens of direct contacts between viral proteins and the host’s molecular machinery.

The work, carried out by scientists at EMBL Hamburg together with partners in Berlin and beyond, was published in Nature Microbiology. It blends a specialised form of cross‑linking mass‑spectrometry (XL‑MS) with a customised AlphaFold modelling pipeline, letting the team capture fleeting, location‑specific protein interactions that had previously escaped detection.

“XL‑MS lets us freeze‑frame the handshake between virus and cell, while AlphaFold tells us exactly which parts are touching,” explained Boris Bogdanow, a junior group leader at Charité’s Institute of Virology. “The result is a structural map that looks like a molecular jigsaw, but with the pieces already snapped together.”

Two major tricks emerged from the map. First, the viral surface protein haemagglutinin was seen slipping through the cell’s transport network, hitching rides on several host proteins that assist its folding and modification – steps that are crucial for the virus to become infectious.

Second, the researchers noticed a striking collapse of paraspeckles – tiny, droplet‑like compartments inside the nucleus that normally help regulate stress responses and antiviral genes. As influenza A spreads, these structures dissolve, freeing RNA‑binding proteins that the virus can then repurpose for its own replication.

“Seeing paraspeckles disappear in every cell line and with every flu strain we tested was a light‑bulb moment,” said first author Iuliia Kotova, now at ETH Zurich. “It isn’t a side‑effect; it looks like a deliberate viral strategy to undermine the cell’s defenses.”

The study relied on an impressive shared infrastructure: XL‑MS experiments ran at Charité, glycoproteomics at EMBL’s proteomics core, AlphaFold modelling on the EMBL compute cluster, and high‑resolution microscopy at the CSSB facility. This collaborative backbone made it possible to move from raw interaction data to a three‑dimensional view of the virus‑host dance.

Looking ahead, the team believes the approach can be rolled out against other pathogens, including high‑risk avian strains such as H5N1. “Each virus has its own set of host levers,” said Jan Kosinski, group leader at EMBL Hamburg. “If we can map those levers in their native cellular context, we’ll have a solid starting point for next‑generation antivirals and smarter vaccines.”