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TitlePolymerase trapping as the mechanism of H5 highly pathogenic avian influenza virus genesis.
Journal, issue, pagesScience, Vol. 391, Page eadr6632-eadr6632, Year 2026
Publish dateMay 20, 2025 (structure data deposition date)
AuthorsMathis Funk / Monique I Spronken / Roy M Hutchinson / Benoit Arragain / Pauline Juyoux / Theo M Bestebroer / Anja C M de Bruin / Alexander P Gultyaev / Ron A M Fouchier / Stephen Cusack / Aartjan J W Te Velthuis / Mathilde Richard /
PubMed AbstractHighly pathogenic avian influenza viruses (HPAIVs) derive from H5 and H7 low pathogenic avian influenza viruses (LPAIVs). Although insertion of a furin-cleavable multibasic cleavage site (MBCS) in ...Highly pathogenic avian influenza viruses (HPAIVs) derive from H5 and H7 low pathogenic avian influenza viruses (LPAIVs). Although insertion of a furin-cleavable multibasic cleavage site (MBCS) in the hemagglutinin gene was identified decades ago as the genetic basis for the LPAIV-to-HPAIV transition, the mechanisms underlying the occurrence of insertion are unknown. Here, we show that transient H5 RNA structures, predicted to trap the influenza virus polymerase on purine-rich sequences, drive nucleotide insertions, providing empirical evidence of RNA structure involvement in MBCS acquisition. Introduction of H5-like sequences and structures into an H6 hemagglutinin resulted in MBCS-yielding insertions. Our results show that nucleotide insertions that underlie H5 HPAIV emergence result from an RNA structure-driven diversity-generating mechanism, which could also occur in other RNA viruses.
External linksScience / PubMed:41818353 / PubMed Central
MethodsEM (single particle)
Resolution1.99 - 2.15 Å
Structure data

PDB-9raf:
Influenza A/H7N9 polymerase in complex with a 70-mer template in stalled elongation with backtracking and stem.
Method: ELECTRON MICROSCOPY / Resolution: 2.15 Å

PDB-9rag:
Influenza A/H7N9 polymerase in complex with a 70-mer RNA template, in stalled elongation.
Method: ELECTRON MICROSCOPY / Resolution: 1.99 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-POP:
PYROPHOSPHATE 2-

Source
  • influenza a virus (a/zhejiang/dtid-zju01/2013(h7n9))
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Influenza polymerase

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