Flu’s ability to withstand fever poses major health risk

Bird flu viruses can replicate at temperatures higher than a typical human fever, resisting one of the body’s defences against infection and posing a serious threat to people, according to research.

A team involving Roslin experts has shed light on how body temperature can affect disease, and identified an influenza virus gene with a role in enabling infection amid feverish conditions.

Until now it has not been clear how fever, which can cause high temperatures, stops viruses – and why some viruses can survive a fever.

The study, led by the Universities of Cambridge and Glasgow, builds on the understanding that some flu viruses can thrive in relatively high temperatures such as the lower respiratory tract, and in the guts of some birds, where temperatures can reach 40-42C. 

Previous studies using cells have shown that avian influenza viruses appear more resistant to temperatures typically seen in fever in humans, of around 40C. 

The latest study, using mice, helps explain how fever protects people, but it may not be enough to safeguard against avian flu.

The team showed that raising the body temperature in mice to levels associated with fever is effective at stopping human-origin flu viruses from replicating, but it is unlikely to stop avian flu viruses. 

Fever protected against severe infection from flu viruses of human origin, with a 2C increase in body temperature enough to dampen a lethal infection into a mild disease.

The research also revealed that a gene of the virus known as PB1, which is known to be important for viral replication, plays a key role in setting viral temperature sensitivity. 

Viruses carrying an avian-like PB1 gene were able to withstand the high temperatures associated with fever, and to cause severe illness.

This is important, because human and bird flu viruses can swap their genes when both viruses infect, for instance, pigs at the same time, raising the prospect of generating new strains of human flu virus infections that are not diminished by fever.

The findings may have implications for the treatment of infections, though the team stresses that more research is needed before changes are considered for treatment guidelines. 

Fever is often treated with anti-fever medication, which includes ibuprofen and aspirin. However, there is clinical evidence that treating fever may not always be beneficial to the patient and may even promote transmission of some flu viruses in humans. 

The research, published in Science, was funded primarily by the Medical Research Council, with additional funding from Wellcome, the Biotechnology and Biological Sciences Research Council, European Research Council, European Union Horizon 2020, UK Department for Environment, Food & Rural Affairs, and US Department of Agriculture.