Fever is one of the human body's key defense mechanisms against viral infections. By increasing body temperature, it slows down or even blocks the replication of many viruses, including seasonal flu. But this natural protection could prove ineffective against certain viruses from the animal world. Researchers from the Universities of Cambridge and Glasgow, in collaboration with institutes in the United States, Japan and Australia, have demonstrated that avian flu viruses manage to multiply despite feverish temperatures.
Their results, published in the journal Science, reveal that these pathogens have a biological advantage that challenges a fundamental immune barrier. In a context where zoonoses are increasing, the thermal resistance of avian influenza represents a concrete risk factor for human health, as illustrated by the first human death linked to the H5N5 virus.
A thermal barrier bypassed by avian viruses
Fever represents one of the oldest and most effective immune responses in mammals. It acts as a thermal barrier, slowing the replication of many pathogens, including human influenza viruses. This mechanism relies on raising body temperature to 41°C. Temperature at which classic viruses struggle to multiply. But this principle does not apply to all viruses. The recent study highlights a worrying exception. Some avian flu viruses are resistant to these high temperatures.
The researchers used a mouse model to simulate a fever in mice infected with different viral strains. Result: if the increase in temperature made it possible to attenuate a human infection, it had no effect against avian strains. This difference is partly explained by the natural environment of aquatic birds, frequent hosts of these viruses. In them, the internal temperature – especially in the intestinal tract – reaches 40 to 42°C. Avian viruses are therefore naturally selected to resist heat.
This ability to bypass a first-line defense represents a significant weakness in our immunity to certain zoonotic viruses. Fever, long considered a protective factor, proves ineffective against these heat-resistant viruses. This questions the relevance of certain treatments, such as antipyretics. And above all, this suggests rethinking our virulence criteria for emerging strains.
The determining role of the PB1 gene in adaptation to heat
At the heart of this thermal resistance, researchers have identified a specific gene from the influenza A virus: PB1. This gene, essential for the replication of the virus's genetic material in infected cells, plays a key role in temperature sensitivity. In their experiments, the Cambridge and Glasgow teams showed that viruses containing a PB1 of avian origin replicated efficiently even at temperatures equivalent to a severe fever.
Human strains, on the other hand, quickly lost their infectious capacity above 39°C. This genetic difference has major implications. The PB1 gene can be exchanged between viral strains when a host (such as a pig) is co-infected with an avian virus and a human virus. This reassortment process was observed during the pandemics of 1957 and 1968. Segments of avian genes were integrated into human strains, making the latter more virulent.
Professor Wendy Barclay, of Imperial College London, points out that this thermal tolerance could explain why certain pandemic strains are particularly aggressive. By allowing replication even in the presence of fever, PB1 of avian origin confers an adaptive advantage to these viruses. It facilitates their dissemination and aggravates the symptoms.
Beyond just temperature, this gene also interacts with host proteins, notably ANP32. They vary depending on the species and influence the activity of the viral polymerase. Understanding these molecular mechanisms would make it possible to anticipate which strains have the highest zoonotic potential. And therefore to better target surveillance and vaccination efforts.
First human cases and warning signs of increased risk
On November 21, 2025, an older adult resident of Washington State died after being infected with the H5N5 virus, a rare strain of avian influenza. According to the Washington State Department of Health and the CDC, this is the first human death caused by this strain. The individual kept domestic birds on his property, and no human-to-human transmission has been detected to date. Nevertheless, this case confirms the passage to humans of an avian virus that has so far been little documented in humans.
Remember that this type of event is not isolated. There are dozens of human cases of avian flu each year, often linked to direct contact with infected birds. But it is these sporadic events that worry virologists. Because once a virus crosses the species barrier, the likelihood of mutations or genetic recombinations increases.
Gustavo del Real, researcher at CSIC (Spain), explains that avian flu can infect different mammals, including humans, when a set of conditions is met. Namely: compatible receptors, favorable environment, and favorable mutations. This phenomenon of “viral promiscuity” specific to influenza A favors the emergence of highly pathogenic strains.
The global H5N1 panzootic, ongoing for several years, has shown the capacity of these viruses to spread massively among birds and to infect mammals, including wild species. We must consider these isolated cases as weak but worrying signals. They remind us that the emergence of a pandemic is often based on a discreet succession of crossings of biological thresholds… Thresholds often detected too late.
Reassessing fever and medical management in the face of emerging viruses
The data from this study call into question a well-established principle: systematically treat fever. If high body temperature represents an effective immune response against classic human viruses, it does not constitute a reliable barrier against heat-resistant avian strains. This has important clinical consequences, particularly on the use of antipyretics (such as ibuprofen or paracetamol).
Previous research has already shown that artificially reducing fever could, in some cases, increase viral load or prolong the duration of infection. However, when faced with a heat-resistant avian virus, these treatments do not slow its spread. Worse, they could weaken other immune defenses.
María Iglesias-Caballero, virologist at the National Center of Microbiology (Spain), recommends using these drugs with discernment. She emphasizes that fever is often seen as a symptom to be suppressed. While it is an integral part of the antiviral regulation system. In the case of viruses insensitive to heat, such as those carrying avian PB1, other levers must be identified to limit viremia (presence of a virus in the blood).
Furthermore, the thermal sensitivity of a virus could become an indicator of virulence to be integrated into epidemiological surveillance models. Systematically testing the fever tolerance of circulating strains would make it possible to identify the most dangerous ones. And especially before they cross the epidemic threshold. This proactive approach could complement genetic surveillance and improve preparedness for future pandemics.
Source: Matthew L. Turnbull et al., “Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals”. Science 390, eadq4691 (2025)
With an unwavering passion for local news, Christopher leads our editorial team with integrity and dedication. With over 20 years’ experience, he is the backbone of Wouldsayso, ensuring that we stay true to our mission to inform.
