The risk of a bird flu pandemic in humans is becoming increasingly worrying. Firstly, because the circulation of this virus is increasing in birds, but also in mammals. But also because the human body would lack the necessary tools to defend itself against it, should this pathogen ever become transmissible between humans. This is particularly true of fever, one of our first lines of defense against infections, but which would be useless against the virus of Avian Flu (H5N1), according to a study published on November 27, 2025 in Science by researchers from the British universities of Glasgow, Cambridge, Oxford and Edinburgh (United Kingdom).
The avian flu virus is accustomed to high temperatures
Let's start with a quick reminder: birds have a higher body temperature than humans. Therefore, it would be perfectly normal for the avian flu virus to be adapted to survive these temperatures, which are normal in birds (up to 42°C), but would be considered a fever in humans. This is especially true in our upper respiratory tract, the entry point for influenza viruses, where the temperature is much lower (around 33°C, compared to 37°C for the lungs).
To verify whether this adaptation to birds made the avian flu virus more resistant to feverish heat in humans, researchers analyzed the virus's ability to replicate in human lung cells at different temperatures. The result: this virus fared well at 37°C, but also at 40°C, whereas the seasonal flu virus struggled to survive at the latter temperature.
Fever alone is not enough to control the infection
This resistance to heat was also observed in vivo. Mice infected with this virus were exposed to high heat (34°C) to mechanically increase their body temperature. This experiment successfully eliminated the influenza virus. seasonal and to protect the animals, but with the avian flu virus, this was no longer enough, and they lost a lot of weight, a sign that the body was unable to control the infection. This could explain the high mortality caused by these viruses in our species: Humans do not tend to be infecteds "Thankfully, we see dozens of cases of avian flu viruses every year, with a very worrying mortality rate of around 401 per 100,000.", underlines in a press release Sam Wilson, researcher at the Institute of Therapeutic Immunology and Infectious Diseases at the University of Cambridge and director of the study.
The protein responsible for this resistance has been identified.
This superpower of avian influenza depends, at least in part, on a fragment of its polymerase, a protein necessary for the transcription and replication of viral RNA. Researchers have identified a segment of this protein, called PB1, the version of which found in the avian influenza virus differs from that of the influenza virus that infects humans. Analyses of the polymerase's activity showed that it was temperature-resistant when it possessed the segment originating from birds. It is therefore thanks to the resistance of this protein, conferred by this PB1 fragment, that this virus can continue to replicate despite fever.
Then, by testing different mutated versions of this segment, the researchers were able to pinpoint the amino acids (the building blocks of proteins) that differ in bird viruses compared to those that infect humans, and which cause this resistance. This knowledge could help us elucidate the mechanisms that allow this protein to become more resistant thanks to these changes: Understanding what allows the avian flu virus to have serious effects on humans is crucial to preparing us for a potential pandemic.Sam Wilson insists.
Fever is a very useful weapon against the seasonal flu virus.
The second conclusion of this study is the importance of fever as a tool in fighting infections. The rise in body temperature was indeed able to quickly control the seasonal flu virus. And this occurred without generating a pro-inflammatory response that could alert the immune system, meaning that it is truly the feverish heat that directly attacks the viruses.
According to the authors, this could partly explain why older people, who have lower body temperatures and a less pronounced febrile response, are more at risk of becoming seriously ill from the seasonal flu virus. They even suggest that fever should be considered more as a normal and protective mechanism (when it is not too high or prolonged). Furthermore, they argue that taking medication to reduce fever during the flu could be counterproductive: it would diminish our innate ability to fight the virus, allowing it to replicate more, which can be detrimental not only to the infected individual but also to those around them, as it would increase the risk of contagion.
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