biostudies-literatureTurnbull MLEuropean Research CouncilMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Councileadq4691https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618609biostudies-literatureUnknown390(6776)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.Science (New York, N.Y.)Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals.PMC7618609BB/P013740/1201366/Z/16/ZMC_UU_12014/10211222101001634Baillie JKLytras SLoney CDavies ELHutchinson EClare STurnbull MLLyons PASmith KGCLee HMWilson SJWilliams SLAlexander AJTWang YNoerenberg MHughes Jda Silva Filipe ASwingler SStewart DGHarcourt KDigard PRihn SJFodor EKapczynski DRTaubenberger JKJung JSCastello AClohisey Hendry SGaunt ERLieber GSmollett KPinto RMfalseAvian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals.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.2025-01-01T00:00:00Z2025 Nov2026-05-29T03:22:34.937Z2026-05-29T03:13:10.687ZS-EPMC76186094130815410.1126/science.adq4691