Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals
Matthew L. Turnbull, Ye Wang, Simon Clare, Gauthier Lieber, Stephanie L. Williams, Marko Noerenberg, Akira J. T. Alexander, Sara Clohisey, Douglas G. Stewart, Joseph Hughes, Simon Swingler, Spyros Lytras, Emma L. Davies, Katherine Harcourt, Katherine Smollett, Rute Maria Pinto, Hui Min Lee, Eleanor Gaunt, Colin Loney, Johanna S Jung, Paul Lyons, Darrell R. Kapczynski, Edward Hutchinson, Ana da Silva Filipe, Jeffery K. Taubenberger, Suzannah J. Rihn, J. Kenneth Baillie, Ervin Fodor, Alfredo Castelló, Kenneth G. C. Smith, Paul Digard, Sam J. Wilson
Abstract
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.