Scientists have discovered that avian influenza viruses possess a unique genome that gives them exceptional resistance to high temperatures. As a result, the human body's natural defense mechanism—fever—proves ineffective in fighting off these infections. In fact, elevated body temperature can even promote the replication of these viruses.

Why Avian Flu Is More Dangerous for Humans

Researchers from the Universities of Cambridge and Glasgow have uncovered why avian flu poses a particular threat to humans compared to seasonal influenza A strains. The key lies in the PB1 gene, which protects the virus from the effects of high temperatures.

Fever is one of the oldest immune responses in mammals. It raises body temperature to slow the reproduction of many pathogens, including influenza A viruses. Seasonal strains adapted to humans replicate best at around 33 °C, typical for the upper respiratory tract, and quickly lose activity when the temperature rises to 40 °C. Birds, however, have a higher body temperature—between 40 and 42 °C—and avian flu viruses have evolved to thrive in these conditions.

The PB1 Genome Experiment

To test whether this genetic feature explains the severity of avian flu infections in humans, scientists engineered nearly identical viruses that differed only in the PB1 gene. In one case, PB1 came from a human strain, which functions poorly at fever-like temperatures; in the other, it was from an avian flu virus, including variants found during the 1957 and 1968 pandemics.

Even a minor genetic change completely altered the virus's behavior, as confirmed in cell cultures and mice. At normal body temperature, both viruses caused severe illness in rodents. However, when body temperature was raised by 2 °C, the human-adapted virus lost its ability to replicate and caused only mild disease. The virus with avian PB1 continued to multiply actively and led to severe illness.

Genetic Exchange and Pandemics

Genetic sequencing has shown that the deadliest flu outbreaks of the 20th century were linked to strains whose PB1 gene originated from birds. Influenza A viruses have eight separate genome segments, and when a cell is infected by two strains at once, these segments can be exchanged (a process called reassortment). PB1 is one of the segments that frequently moves between human and avian viruses.

Dr. Matt Turnbull from the MRC-University of Glasgow Centre for Virus Research notes that the ability of viruses to swap genes is a constant source of new flu strains. Such exchanges have already led to severe pandemics, such as in 1957 and 1968, when the human virus acquired PB1 from an avian strain.

Implications for Monitoring and Prevention

The findings suggest that this small gene allowed viruses to bypass the human body's temperature defense and cause devastating infections during past pandemics. It could become a problem again if avian flu viruses learn to spread efficiently among people.

Turnbull emphasizes the importance of monitoring avian flu strains to prepare for potential outbreaks. Testing potential viruses for fever resistance could help identify more dangerous variants in advance.

Current Situation and Risks

Last month, a fatal case of infection with a new avian flu strain, previously unseen in humans, was reported in Washington state. So far, avian flu viruses have not developed the ability to spread efficiently between people, so only isolated cases are recorded, which typically result in severe illness.

Professor Sam Wilson from the University of Cambridge points out that avian flu mortality in humans has always been a serious concern—for example, historical H5N1 infections have had a fatality rate exceeding 40%. Understanding why avian flu causes such severe disease in humans is crucial for monitoring and preparing for possible pandemics, especially given the threat posed by H5N1 viruses.

The study was published in the journal Science.