EMBL Maps Influenza Virus Rewiring of Human Cells

Researchers at EMBL Hamburg and the Leibniz Research Institute for Molecular Pharmacology (FMP) have mapped how the influenza A virus rewires infected human cells in unprecedented detail. Published in Nature Microbiology on 20 July 2026, the work marks the first time scientists have mapped direct virus-host protein contacts at scale inside intact influenza-infected cells, with enough structural detail to model how viral and human proteins fit together.

The team combined a specialised version of cross-linking mass spectrometry (XL-MS), developed by Boris Bogdanow and Fan Liu at FMP Berlin, with a modified AlphaFold protein structure prediction workflow developed by Jan Kosinski’s group at EMBL Hamburg. Unlike earlier biochemical methods that required cells to be broken open before interactions could be measured, XL-MS captures protein-protein interactions directly inside intact infected cells, preserving short-lived and location-specific contacts. The team traced how haemagglutinin, the influenza surface protein that binds and enters host cells, moves through the cell’s internal transport and processing system, revealing previously unknown host proteins that help the virus correctly fold and modify haemagglutinin.

The second finding was that influenza A infection causes paraspeckles, small droplet-like compartments in the cell nucleus, to dissolve. This consistently occurred across every cell line and every flu strain tested, releasing RNA-binding proteins for the virus to co-opt for replication. Paraspeckles have also been implicated in cellular stress responses and antiviral gene regulation, so their disruption may weaken part of the host cell’s defence response. Bogdanow described the workflow as broadly applicable to viruses of potential pandemic relevance including H5N1.

The commercial signal cuts two ways. On the drug discovery side, the newly identified host proteins involved in haemagglutinin trafficking and paraspeckle dissolution offer concrete druggable targets for host-directed antiviral development. On the platform side, the combined XL-MS plus AlphaFold workflow adds a differentiated capability for virus-host interaction mapping. Expect early interest from pandemic preparedness programmes and antiviral pipelines at Roche, GSK and Moderna.

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