A new study has created a detailed molecular map of how influenza A hijacks human cells, exposing interactions that could guide future antiviral and vaccine research.
How does the influenza virus take control of a human cell and turn its machinery into a system for producing more viruses?
Researchers at EMBL Hamburg and the Leibniz Research Institute for Molecular Pharmacology have mapped direct interactions between influenza A proteins and human proteins inside intact infected cells.
The study provides unprecedented structural detail about where viral and host proteins come into contact and how these interactions may help the virus replicate.
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Influenza
Influenza, commonly called the flu, is a contagious respiratory infection caused by influenza viruses. It can cause mild to severe illness, with symptoms such as sudden fever, cough, sore throat, headache, body aches and fatigue.(1✔ ✔Trusted Source
Influenza (seasonal)
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Influenza A and B viruses cause seasonal epidemics, while influenza A is the only type known to cause pandemics. Seasonal influenza produces around one billion infections and 3–5 million severe cases annually, leading to an estimated **290,000–650,000 respiratory dearn560660search19.
After entering a host cell, influenza A releases its RNA, which contains the instructions needed to produce viral proteins. These proteins redirect the cell’s molecular machinery, allowing the virus to copy its genetic material and assemble new virus particles.
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Scientists Map Flu–Human Protein Contacts Inside Cells
Previous protein-interaction studies often required researchers to break cells open before analysis. This could remove cellular compartments, destroy fragile interactions or cause proteins that never met inside the cell to mix in laboratory samples.(2✔ ✔Trusted Source
Mapping in-cell protein contact sites reveals hijacking of paraspeckles during influenza A virus infection
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The researchers overcame this problem by using a specialised form of cross-linking mass spectrometry, known as XL-MS. The technique chemically connects proteins that are close together inside an intact infected cell, preserving short-lived and location-specific interactions.
Jan Kosinski of EMBL Hamburg said the method enables researchers to study flu-host interactions.
The team combined these experimental measurements with computational structural modelling. A modified form of AlphaFold used the cross-linking data as spatial constraints, helping predict how viral and human proteins physically fit together.
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Influenza Reshapes Protein Processing and Nuclear Structures
The molecular map revealed two important ways in which influenza A reorganises the infected cell.
First, researchers examined haemagglutinin, a viral surface protein that enables influenza to attach to and enter host cells. They identified human proteins involved in folding, modifying and transporting haemagglutinin through the endoplasmic reticulum and Golgi system.
Second, the virus caused the progressive breakdown of paraspeckles, small RNA–protein compartments inside the cell nucleus. This effect was observed across several human cell lines and influenza strains.
Paraspeckles help organise RNA-binding proteins and may participate in cellular stress responses and antiviral gene regulation.(2✔ ✔Trusted Source
Mapping in-cell protein contact sites reveals hijacking of paraspeckles during influenza A virus infection
When influenza dissolves these structures, the released proteins may become available for the virus to use during replication. Their disruption could also weaken some of the cell’s natural defence mechanisms.
The consistent response across the tested cells suggested that paraspeckle disassembly may represent a deliberate viral strategy rather than an accidental consequence.
Findings May Reveal Future Antiviral Targets
By identifying exactly where influenza proteins connect with human proteins, the approach may help scientists locate molecular interactions that could be disrupted by future antiviral drugs.
However, the findings do not immediately provide a new treatment or vaccine. The current results represent a snapshot from a particular stage of infection and were obtained using a laboratory-adapted influenza strain.
Further studies must examine how these interactions change throughout the infection cycle and whether the same mechanisms occur with clinically important or emerging viruses.
The researchers believe the workflow could eventually be applied to influenza strains with pandemic potential, including H5N1, as well as other viruses that hijack human cells.
References:
- Influenza (seasonal)- (https://www.who.int/news-room/fact-sheets/detail/influenza-%28seasonal%29?)
- Mapping in-cell protein contact sites reveals hijacking of paraspeckles during influenza A virus infection-(https://www.nature.com/articles/s41564-026-02416-1)
Source-Medindia