Avian flu viruses are a huge threat to humans because they can replicate even at temperatures higher than those of fever, which is the human body’s main weapon to combat the attack of viruses.
This is according to an international investigation, led by the universities of Cambridge and Glasgow (United Kingdom), whose details were published this Thursday in Science.
The study, carried out with cell cultures and mouse models, has identified an avian gene that allows viruses to resist the high temperatures of human fever and that passed to human flu viruses in the 1957 and 1968 pandemics, the deadliest after that of 1918.
Each year, human flu viruses cause millions of infections. The most common – those that cause seasonal flu – are influenza A, which infect the upper respiratory tract, where the temperature is around 33º C, instead of in the deep lungs (the temperature reaches 37º C).
The virus replicates and spreads through the body causing an illness that can be serious. To defend itself, our body activates fever, a self-defense mechanism that can raise body temperature to 41ºC.
But until now it was unclear how fever stops viruses and why some can survive.
For their part, avian flu viruses usually thrive in the lower respiratory tract and in some hosts, such as ducks and seagulls, they infect the intestine, where temperatures are around 40º and 42º C. That is, avian viruses are more resistant to the temperatures typical of fever in humans.
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Mouse models
Previous studies with cultured cells showed that avian flu viruses appear more resistant to the temperatures typical of human fever. The study published today in Science attempted to explain how fever protects us and why it may not be enough against avian viruses.
To do this, they used mouse models infected with PR8 influenza virus, a strain of H1N1 influenza virus adapted to cause severe illness in mice, and conducted scientific studies.
The researchers raised the body temperature of the animals (mice do not naturally develop fever) to see how flu viruses responded and showed that fever is effective in stopping the replication of human flu viruses, but is unlikely to stop bird flu viruses.
Fever protected against severe human flu infections, with only a 2°C rise in body temperature turning a lethal infection into a mild illness.
The research also revealed that the virus’s PB1 gene, important in replicating the virus genome within infected cells, is key in determining temperature sensitivity.
Viruses carrying this avian-type gene were able to withstand the high temperatures associated with fever, and caused severe disease in mice. This is important, because human and avian flu viruses can ‘swap’ genes when they co-infect a host at the same time, the study warns.
“The ability of viruses to exchange genes is a continuing source of threat to emerging influenza viruses. We have seen this in previous pandemics, such as those of 1957 and 1968, where a human virus exchanged its PB1 gene for that of an avian strain. This may help explain why these pandemics caused serious illness in people,” says Matt Turnbull, first author of the study and researcher at the University of Glasgow.
For Turnbull “it is crucial” to monitor bird flu strains to anticipate possible outbreaks and identify the most virulent strains.
Along the same lines, the lead author, Sam Wilson, from the Institute of Therapeutic Immunology and Infectious Diseases at the University of Cambridge, recalls that although fortunately humans do not usually become infected with avian flu viruses very frequently, there are dozens of cases a year.
“Understanding what causes avian influenza viruses to cause severe disease in humans is crucial for pandemic preparedness and surveillance efforts. This is especially important given the pandemic threat posed by H5N1 avian viruses.”
Although the findings may have implications for treating infections, the team stresses that more research is needed before changes to treatment guidelines are considered.
Fever is often treated with antipyretic medications, such as aspirin or ibuprofen, but there is clinical evidence that treating fever may not always be beneficial to the patient, but may even promote the transmission of influenza A viruses in humans.
With information from EFE
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