Researchers report an in-cell, residue-level interaction map between influenza A proteins and human proteins, outlining how infection can disrupt nuclear paraspeckles and potentially release host factors that support viral replication.
Researchers based at EMBL Hamburg, working with collaborators at the Leibniz Research Institute for Molecular Pharmacology (FMP), have reported a high-resolution map of contacts between influenza A virus proteins and human proteins inside infected cells.
Using in-cell cross-linking mass spectrometry on intact infected human lung epithelial cells, the team identified hundreds of virus–host protein pairs and combined those measurements with AlphaFold-based structural modelling to infer where proteins contact one another.
Among the findings, the study links influenza A infection to disruption of paraspeckles—membraneless structures in the cell nucleus built around the long non-coding RNA NEAT1. The authors report that viral proteins interact with paraspeckle components and that a viral endonuclease, PA-X, contributes to paraspeckle disruption by degrading NEAT1, a change that releases host factors that the study says can facilitate influenza A replication.
“Watching these tiny organelles in the nucleus dissolve, consistently across every cell line and every flu strain we tested, told us this isn't a side effect of infection – it might be a strategy,” said first author Iuliia Kotova in a statement accompanying the work.
The results were published in Nature Microbiology. The researchers said the interaction map could help guide future studies of influenza biology, including work relevant to strains of concern such as H5N1.
