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New research published today in Science reveals a critical vulnerability in human defenses against bird flu, explaining why avian influenza viruses pose a persistent pandemic threat. Scientists at the universities of cambridge and Glasgow have discovered that bird flu viruses can replicate effectively at temperatures higher than those typically associated with a human fever – a natural defense mechanism designed to halt viral spread.
The Fever Paradox: Why Some Viruses Survive
For years, the precise mechanism by which fever combats viruses has remained unclear. The body raises its core temperature, sometimes to as high as 41C (105.8F), as a defense strategy. However, this new study illuminates why this strategy isn’t foolproof. Researchers found that the temperature sensitivity of a virus is dictated by a single gene, a key factor in past pandemics.The research team highlighted that the critical gene responsible for temperature sensitivity transferred into human flu viruses during the deadly pandemics of 1957 and 1968, allowing those strains to proliferate.
“We’ve seen it happen before,” stated a senior researcher involved in the study. “Human and bird flu viruses can ‘swap’ genes when they co-infect a host, like a pig, and this can have devastating consequences.” This gene swapping ability remains a important threat, constantly creating the potential for new, virulent strains.
Mouse models Reveal Key Insights
To understand this phenomenon, the international research team simulated fever conditions in mice infected with influenza viruses. While mice don’t naturally develop fevers in response to influenza A, researchers successfully elevated thier body temperature to mimic the effect. The results were striking: raising body temperature effectively stopped human-origin flu viruses from replicating, turning a perhaps lethal infection into a mild illness with just a 2C (3.6F) increase. However, avian flu viruses proved far more resilient.
The study pinpointed the PB1 gene as the key player in determining temperature sensitivity. Viruses carrying an avian-like PB1 gene were able to withstand the high temperatures associated with fever, causing severe illness in the mice. This finding underscores the importance of monitoring bird flu strains for their potential to overcome the body’s natural defenses.
Implications for Treatment and Pandemic Preparedness
The findings have potential implications for the treatment of influenza, even though researchers caution that further investigation is needed before altering current guidelines. currently, fever is frequently enough treated with antipyretic medications like ibuprofen and aspirin. however, clinical evidence suggests that suppressing fever may not always be beneficial and could even promote the transmission of influenza A viruses.
“Understanding what makes bird flu viruses cause serious illness in humans is crucial for surveillance and pandemic preparedness efforts,” explained Professor Sam Wilson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge. “This is especially important because of the pandemic threat posed by avian H5N1 viruses.”
Dr. Matt Turnbull, first author of the study from the Medical Research Council Center for Virus Research at the University of Glasgow, emphasized the need for proactive monitoring. “It’s crucial that we monitor bird flu strains to help us prepare for potential outbreaks. Testing potential spillover viruses for how resistant they are likely to be to fever may help us identify more virulent strains.”
The research was funded by the Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences research Council, European Research Council, European Union Horizon 2020, UK Department for Habitat, Food & Rural Affairs, and US Department of Agriculture.
Source: Turnbull, M. L., et al. (2025) Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in Mammals. Science. DOI: 10.1126/science.adq4691. https://www.science.org/doi/10.1126/science.adq4691
