Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
Authors: Alymova Irina V, York Ian A, McCullers Jonathan A
Journal: PloS one
Summary
# Editorial Summary: PB1-F2 Virulence Markers in Mammalian Influenza A Viruses The PB1-F2 protein—expressed from an alternative reading frame within the influenza A virus genome—contains specific amino acid residues that enhance both inflammatory responses and direct cytotoxicity, and evidence from mouse models demonstrates these variants substantially increase disease severity during both primary viral and secondary bacterial infections. Alymova and colleagues screened PB1-F2 sequences from influenza viruses circulating in pigs, horses, and dogs to determine whether mammalian species in close human contact might harbour particularly virulent strains, identifying all four key inflammatory residues (L62, R75, R79, L82) across these species and discovering the cytotoxic marker I68 was especially common in equine and canine isolates. Notably, approximately 75% of equine influenza viruses and 20% of canine viruses contained combinations of multiple virulence-associated residues, compared to only 7% of swine viruses—suggesting horses represent an underappreciated reservoir for pathogenic PB1-F2 variants. For equine professionals, this finding underscores the importance of robust biosecurity practices and prompt reporting of respiratory disease outbreaks, as equine influenza viruses carrying these molecular markers could theoretically pose zoonotic risks during reassortment events. Enhanced surveillance protocols targeting genetic markers of virulence in circulating equine strains would strengthen pandemic preparedness frameworks and improve our capacity to detect emerging threats before they become established in human populations.
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Practical Takeaways
- •Equine influenza poses a potential zoonotic risk due to genetic markers associated with enhanced virulence; veterinarians should remain vigilant for emerging strains with pandemic potential.
- •Surveillance protocols for equine influenza should include molecular characterization of PB1-F2 segments to identify virulence-associated residues that may signal heightened pandemic risk.
- •Horses warrant closer monitoring in influenza pandemic preparedness planning, given their higher prevalence of virulence markers compared to other mammalian reservoirs.
Key Findings
- •Equine influenza A viruses carry virulence-associated PB1-F2 residues in approximately 75% of historical strains, with high frequency of both inflammatory (L62, R75, R79, L82) and cytotoxic (I68, L69, V70) markers.
- •All four inflammatory residues were identified in PB1-F2 proteins from equine IAVs, with I68 cytotoxic residue being especially prevalent.
- •Horses represent an important reservoir for pathogenic PB1-F2 variants alongside birds and pigs, with potential implications for pandemic preparedness.
- •Equine IAVs historically showed higher prevalence of virulence-associated residue combinations (75%) compared to swine IAVs (7%).