Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals
et al., Science, doi:10.1126/science.adq4691, Nov 2025
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In vitro and mouse study showing the benefit of elevated body temperature against human-adapted influenza A viruses, and that avian-origin PB1 polymerase subunits overcome this natural defense. Authors found that the avian-origin PB1 protein enables viral replication at higher temperatures (40°C), a trait adapted from birds. In mice, simulating a fever by raising the ambient temperature successfully protected the animals from severe disease caused by a human-origin strain (PR8). However, an engineered virus with an avianized PB1 mutant bypassed this temperature-based immunity, causing severe disease despite the hyperthermic state. Authors suggest that this fever-resistant replication explains why certain pandemic strains that acquired avian-origin PB1 caused more severe disease in humans.
3 preclinical studies support the efficacy of thermotherapy for COVID-19:
1.
Xie et al., Molecular Basis of High-Blood-Pressure-Enhanced and High-Fever-Temperature-Weakened Receptor-Binding Domain/Peptidase Domain Binding: A Molecular Dynamics Simulation Study, International Journal of Molecular Sciences, doi:10.3390/ijms26073250.
Turnbull et al., 27 Nov 2025, peer-reviewed, 32 authors.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
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"abstract": "<jats:p>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.</jats:p>",
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