There are growing concerns over the threat of avian flu to humans amid a breakthrough on why they have such a high mortality rate.

New study led by the University of Cambridge and the University of Glasgow has issued new warnings that bird flu viruses are a major threat to humans. It explained bird flu viruses are a particular threat to humans because they can replicate at temperatures higher than a typical fever, one of the body’s ways of stopping viruses in their tracks.

The team’s study identified a gene that plays an important role in setting the temperature sensitivity of a virus. In the deadly pandemics of 1957 and 1968, this gene transferred into human flu viruses, and the resulting virus thrived.

It added: “Human flu viruses cause millions of infections every year. The most common types of these viruses, which cause seasonal flu, are known as influenza A viruses.

“They tend to thrive in the upper respiratory tract, where the temperature is around 33C, rather than deep in the lungs in the lower respiratory tract, where the temperature is around 37C.

“Unchecked, a virus will replicate and spread throughout the body, where it can cause illness, occasionally severe. One of the body’s self-defence mechanisms is fever, which can cause our body temperature to reach as high as 41C.”

Dr Matt Turnbull, the first author of the study, from the MRC Centre for Virus Research at the University of Glasgow said: “The ability of viruses to swap genes is a continued source of threat for emerging flu viruses. We’ve seen it happen before during previous pandemics, such as in 1957 and 1968, where a human virus swapped its PB1 gene with that from an avian strain. This may help explain why these pandemics caused serious illness in people.

“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.”

Unlike human flu viruses, avian influenza viruses tend to thrive in the lower respiratory tract. In fact, in their natural hosts, which include ducks and seagulls, the virus often infects the gut, where temperatures can be as high as 40 to 42C.

The research also revealed that the PB1 gene of the virus, important in the replication of the virus genome inside infected cells, plays a key role in setting the temperature-sensitivity.

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

This is important, because human and bird flu viruses can ‘swap’ their genes when they co-infect a host at the same time, for example when both viruses infect pigs.

Senior author professor Sam Wilson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, added: “Thankfully, humans don’t tend to get infected by bird flu viruses very frequently, but we still see dozens of human cases a year. Bird flu fatality rates in humans have traditionally been worryingly high, such as in historic H5N1 infections that caused more than 40% mortality.

“Understanding what makes bird flu viruses cause serious illness in humans is crucial for surveillance and pandemic preparedness efforts. This is especially important because of the pandemic threat posed by avian H5N1 viruses.”