Mutations that might help bird flu viruses cross to humans are present in many of the strains of the H5N1 virus currently causing mass outbreaks in wild birds – although more genetic changes would be needed to cause a pandemic in people.
The finding stems from the discovery of a human immune system protein that is usually important in stopping bird flu from infecting people.
In the four flu pandemics of the 20th and 21st centuries, the viruses had genes that meant they could overcome the newly discovered antiviral protein. While such mutations aren’t sufficient to cause a pandemic, “the less we see of them, the better”, says Massimo Palmarini at the University of Glasgow, UK.
The current bird flu outbreak, involving a subtype called H5N1, has been circulating in wild birds in huge numbers since about 2021 and has caused mass die-offs of threatened species, such as Dalmatian pelicans in Greece.
It has also affected farmed poultry and mammals that prey on birds, and there have been a few cases in people, but so far it hasn’t evolved the ability to spread easily between mammals – so there is intense interest in understanding how likely that possibility is.
Palmarini and his colleagues have shed light on this question by looking at flu viruses growing in cells in a dish. They studied an antiviral protein called butyrophilin, which is present in cells of the airways and lungs and comes in slightly varying forms in different mammalian species. They found that the human version stops most bird flu viruses from reproducing.
The human form of butyrophilin seems to have evolved about 40 million years ago and helps to protect all primates from catching flu viruses that are adapted to birds. It doesn’t, however, stop humans and other primates from catching other forms of influenza.
Palmarini’s team also looked at genetic sequences of the viruses that caused past flu pandemics in humans, some of which derived from bird flu. The 1918 flu pandemic, which crossed into people from birds, had mutations that meant it could beat the human version of butyrophilin. The flu pandemics of 1957 and 1968 and the 2009 “swine flu” pandemic contained human flu or pig flu virus genes that could also overcome butyrophilin.
Mutations similar to those in the 1918 virus have been seen in about half of the H5N1 viruses causing the current outbreak in wild birds, as well as in nearly all of the cases that occurred in people, says Rute Maria Pinto, who also worked on the study at the University of Glasgow.
None of the human cases have led to widespread transmission in people, however, showing that further mutations or swapping of genes with other viruses is probably necessary for that to happen, says Wendy Barclay at Imperial College London. “Thankfully, we are still not seeing lots of spillovers,” she says. “But I’d be sleeping easier at night if there were lots of barriers for this virus to overcome. It’s already overcome this one.”
In May, a report from the UK Health Security Agency concluded that the current H5N1 viruses don’t seem to spread easily to people and there had been no evidence of human to human transmission so far.
Scientists who monitor the risk from circulating flu viruses are already monitoring for the presence of mutations that would let these viruses overcome butyrophilin, says Barclay.