Bird Flu Virus Might Resist Fever, Study in Mice Finds

Running a temperature helps humans protect themselves from infections, but research testing avian flu viruses in mice suggests these strains share a trait with those that caused some of the world’s worst pandemics: the ability to resist a fever. Though more research is needed to see if the findings can be replicated and extrapolated to humans, the results suggest that this trait enables viruses to continue sickening their hosts, increasing the threat of severe disease in humans.

A study published in the journal Science finds that bird flu viruses, which have adapted to tolerate temperatures of 40 to 42 degrees Celsius — 104 to 107 degrees Fahrenheit — can resist fever-like temperatures in mice. Breaking through the fever barrier, the researchers say, is one reason a virus could continue to replicate, worsening disease symptoms in its host.

The findings, the researchers say, suggest that while fevers would help people defend against human-adapted seasonal flu viruses like H1N1 and H3N2, they might not stop an avian-origin virus like H5N1, a strain that has already jumped to humans and killed about half of those it has infected, although person-to-person transmission has not been recorded.

As of November 5, 2025, the World Health Organization says, globally, there have been 992 cases of human infection with H5N1 since January 2003. Of those 476 were fatal.

Fevers are one way humans protect themselves from viral infections. A virus’s ability to resist fever does not make a pandemic more likely, the researchers said, but may mean that people are likely to experience worse sickness if they are infected.

Influenza viruses are divided into four categories, from A to D. The new study focused on influenza A viruses, a category that includes H5N1 and other subtypes known to cause flu pandemics.

Because of the numerous jumps it has already made, to people, marine mammals like seals and sea lions and land animals like dairy cattle, H5N1 is particularly worrying scientists. “It seems to be spreading around the globe very well and we’re seeing lots of introductions into mammals. And we’re quite worried about this because once the virus crosses into mammals, it has an opportunity to pick up mutations that might make it better in humans, which is our ultimate concern,” says Matt Turnbull, a doctor at the University of Glasgow’s Medical Research Council Centre for Virus Research and the study’s lead author.

The ability of avian-origin flus to resist fever suggests that if a strain like H5N1 began to spread widely in humans, the consequences might be comparable to some of history’s worst pandemics. “In the worst influenza pandemics that we know about, from 1918, 1957 and 1968, all of these pandemics received genetic material from avian influenza viruses that increase the ability of these viruses to replicate at human febrile temperatures,” says the study’s senior author, Sam Wilson, a professor at the University of Cambridge’s Institute of Therapeutic Immunology and Infectious Disease.

A human febrile temperature, or fever, is generally defined as anything higher than 37 degrees Celsius or 98.6 degrees Fahrenheit. The so-called ‘Spanish flu’ pandemic of 1918, killed an estimated 50 million people. The 1957 ‘Asian flu’ pandemic killed an estimated 1.1 million and the 1968 ‘Hong Kong flu’ pandemic killed one to four million.

Wilson cautioned, however, that although the virus’s ability to overcome a fever defense could make a pandemic more severe, because the disease could be more severe, he does not think “it inherently increases or decreases the risk of a pandemic occurring.”

During the same study, the researchers identified a gene called PB1 that plays an evolutionary role in setting the temperature, lower or higher, at which influenza A viruses replicate. “If they’ve been in hot birds in the recent past, then they’re adapted to high temperatures. And if they’ve been in cool humans in the recent past, then they tend to be adapted to lower temperatures,” says Wilson.

To test fever responses, the mice used in the study, which came from Charles River Laboratories, were infected with a temperature-resistant PB1-mutant virus using a nasal spray. Because mice do not usually develop fevers in response to influenza A viruses, the researchers gradually raised the temperature in their enclosures to simulate a fever.

None of the infected mice were allowed to die of flu, but they did lose weight, a sign of sickness. A control group that was not infected with the virus, but were kept at the same higher temperatures, did not suffer weight loss, explains Turnbull. Infected mice that lost 25% of their body weight were killed by cervical dislocation, which separates the spinal cord from the brain. Had they not been killed, the researchers predict they would have died of flu.

While clinical trials in humans would be needed before extrapolating a study of mice to people, Wilson believes the study’s findings could mean medications used to lower fever might end up making people with seasonal flu sicker and more likely to infect others because the virus would continue to replicate, when a higher fever might help stop replication. Conversely, those who have caught an influenza virus directly from a bird might want to bear in mind that allowing a fever to run its course might not have the same beneficial effect. Though they stress people should listen to the advice of medical professionals if they get sick. Meghan Frost Davis, an associate professor at the Johns Hopkins’ Department of Health and Engineering who was not involved with the study, agreed that the findings suggest that bird flu’s ability to bypass a fever defense could mean that a greater proportion of people infected with these strains get sicker. If a strain of bird flu becomes capable of human-to-human transmission, and if it retains this fever bypass trait, “then it could contribute to more common or more severe disease on average,” she tells Sentient in an email.

“Remember ‘flatten the curve’ during COVID? When a virus is more severe, more people end up needing advanced support (ventilators, ICU-level care), which is in limited supply,” she writes. “More severe disease can mean not just more people die, but also a far greater burden on the healthcare system, which then has carry-on effects on patient care as a whole.”