Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals
- Matthew L. Turnbull
- Yingxue Wang
- Simon Clare
- Gauthier Lieber
- Stephanie L. Williams
- Marko Noerenberg
- Akira J. T. Alexander
- Sara Clohisey Hendry
- Douglas G. Stewart
- Joseph Hughes
- Simon Swingler
- Spyros Lytras
- Emma L. Davies
- Katherine Harcourt
- Katherine Smollett
- Rute M. Pinto
- Hui Min Lee
- Eleanor R. Gaunt
- Colin Loney
- Johanna S. Jung
- Paul A. Lyons
- Darrell R. Kapczynski
- Edward Hutchinson
- Ana da Silva Filipe
- Jeffery K. Taubenberger
- Suzannah J. Rihn
- J. Kenneth Baillie
- Ervin Fodor
- Alfredo Castello
- Kenneth G. C. Smith
- Paul Digard
- Sam J. Wilson
2025-11-27
Host body temperature can define a virus’s replicative profile—influenza A viruses (IAVs) adapted to 40° to 42°C in birds are less temperature sensitive in vitro compared with human isolates adapted to 33° to 37°C. In this work, we show that avian-origin PB1 polymerase subunits enable IAV replication at elevated temperatures, including avian-origin PB1s from the 1918, 1957, and 1968 pandemic viruses. Using a model system to ensure biosafety, we show that a small increase in body temperature protects against severe disease in mice and that this protection is overcome by a febrile temperature–resistant PB1. These findings indicate that although elevated temperature itself can be a potent antiviral defense, it may not be effective against all influenza strains. These data inform both the clinical use of antipyretics and IAV surveillance efforts.