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Scientists Produce First Structural In‑Cell Map of Influenza A–Host Protein Contacts

Researchers paired in‑cell cross‑linking mass spectrometry with a modified AlphaFold pipeline to identify host factors that help fold the viral haemagglutinin.

Overview

  • A peer‑reviewed paper published in Nature Microbiology reports the first large‑scale, structurally informed map of direct protein contacts between influenza A and human host proteins inside intact infected cells.
  • The team used a specialised in‑cell cross‑linking mass spectrometry (XL‑MS) workflow and fed the cross‑link data into a modified AlphaFold modelling pipeline to predict how viral and host proteins fit together.
  • Experiments traced haemagglutinin through the cell’s secretory pathway and identified specific host proteins that assist its folding and glycoform maturation, revealing possible drug targets.
  • The study found that influenza A infection causes nuclear paraspeckles to dissolve, releasing RNA‑binding proteins the virus appears to repurpose for replication, a mechanism observed across multiple cell lines and strains tested in the lab.
  • Work relied on shared facilities across EMBL, FMP and Charité and the authors say the ‘mapping in context’ approach can be applied to other viruses but requires testing on diverse strains, infection stages, and functional follow‑ups before clinical translation.