tetano
Editor, Senior Moderator
Science
. 2026 Mar 12;391(6790):eadr6632.
doi: 10.1126/science.adr6632. Epub 2026 Mar 12.
Polymerase trapping as the mechanism of H5 highly pathogenic avian influenza virus genesis
Mathis Funk[SUP] 1 [/SUP], Monique I Spronken[SUP] 1 [/SUP], Roy M Hutchinson[SUP] 1 [/SUP], Benoit Arragain[SUP] 2 [/SUP], Pauline Juyoux[SUP] 3 [/SUP], Theo M Bestebroer[SUP] 1 [/SUP], Anja C M de Bruin[SUP] 1 [/SUP], Alexander P Gultyaev[SUP] 1 4 [/SUP], Ron A M Fouchier[SUP] 1 [/SUP], Stephen Cusack[SUP] 2 [/SUP], Aartjan J W Te Velthuis[SUP] 5 [/SUP], Mathilde Richard[SUP] 1 [/SUP]
Affiliations
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.
. 2026 Mar 12;391(6790):eadr6632.
doi: 10.1126/science.adr6632. Epub 2026 Mar 12.
Polymerase trapping as the mechanism of H5 highly pathogenic avian influenza virus genesis
Mathis Funk[SUP] 1 [/SUP], Monique I Spronken[SUP] 1 [/SUP], Roy M Hutchinson[SUP] 1 [/SUP], Benoit Arragain[SUP] 2 [/SUP], Pauline Juyoux[SUP] 3 [/SUP], Theo M Bestebroer[SUP] 1 [/SUP], Anja C M de Bruin[SUP] 1 [/SUP], Alexander P Gultyaev[SUP] 1 4 [/SUP], Ron A M Fouchier[SUP] 1 [/SUP], Stephen Cusack[SUP] 2 [/SUP], Aartjan J W Te Velthuis[SUP] 5 [/SUP], Mathilde Richard[SUP] 1 [/SUP]
Affiliations
- PMID: 41818353
- DOI: 10.1126/science.adr6632
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.