A new study by biologists from the Scripps Research Institute shows that a bird flu virus is just a single mutation away from having human-ready receptors.
If the H5N1 virus does make the switch, it could lead to widespread infection rates in humans.
Thus far, the virus has been limited in humans.
According to a new study published in the journal Science by Scripps Research Institute biologists, the avian H5N1 virus has the potential to quickly shift from a bird flu to a human flu. The authors wrote that the pathogen, which first popped up in North America in 2021, is just a “single mutation” away from being able to infect humans with the same efficacy it can currently infect other animals.
“In nature, the occurrence of this single mutation could be an indicator of human pandemic risk,” according to an editorial note attached to the paper. The study showed that just one mutation—the amino acid glutamine transforming into leucine, specifically at “residue 226 of the virus hemagglutinin”—was enough to make the switch from avian to human.
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According to the Los Angeles Times, study coauthor James Paulson said that the discovery “really surprised us.” And Richard Webby, director of the World Health Organization’s Collaborating Center for Studies on the Ecology of Influenzas in Animals and Birds, who was not involved in the study, said that this news “will likely cause a stir. I think most of us thought it would probably need more than one change.”
Each virus has a certain kind of cell that it is best at infecting. In order to latch onto a host, that host has to have the proper receptors for the virus to attach to. Birds and humans have different receptors on their cells, which means that a virus requires just the right match to pick the lock of the cell, so to speak, to be easily transferrable.
Since its discovery in 2021, the H5N1 virus has been able to bond with receptors in avian species, marine mammals, and even (occasionally) humans. By 2024, that virus was spreading widely in the country’s dairy cattle population, causing mild cases in over 50 people.
Those human infections raised concerns about the capability for bovine-to-human (or even human-to-human) transmission, despite the fact that the virus was still best suited to avian receptors. The concern, understandably, is the potential for a pandemic if the disease becomes broadly and easily transmissible to and between humans.
“For a new pandemic H5N1 virus, we know that it has to switch receptor specificity from avian-type to human-type,” the study authors wrote. “So, what will it take?” Apparently, just one mutation.
“The initial infection is what we’re concerned about to initiate a pandemic,” Paulson said, according to Scientific American, “and we believe that the weak binding that we see with this single mutation is at least equivalent to a known human pandemic virus.”
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The Paulson-led research team synthesized the genetic sequence for the strain of bird flu found in a Texas dairy worker—the first human known infected with the H5N1 virus—and then examined proteins on the outer surface of the virus, where it links to the cell membrane of its host. To find the right docking equipment, so to speak, the team researched past examples of the avian flu jumping to humans, and found that a change from glutamine to leucine in position 226 would switch the virus into a mode compatible with easily infecting human biology.
Many of the human cases of the virus came from dairy workers repeatedly exposed to the virus, which likely overpowered the cells by entering through the eyes and nose in great numbers. For a quick and easy spread, the virus must transmit via infected droplets traveling in the air from a sneeze or cough. “In this context, the virus needs to be able to recognize human-type receptors to bind to cells in the human airway in amounts sufficient to cause infection,” Paulson said.
While this hasn’t yet happened in the H5N1, it has occurred in the past. And if the change does occur now, it could spark a quick-moving avian flu virus ready-made for humans to pass along to one another.
Plenty of variables remain—including whether this mutation will ever even occur—and predicting the severeness or concern over the H5N1 is only speculative. But it’s good to know what we’re up against, should that one little switch occur.
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Tim Newcomb is a journalist based in the Pacific Northwest. He covers stadiums, sneakers, gear, infrastructure, and more for a variety of publications, including Popular Mechanics. His favorite interviews have included sit-downs with Roger Federer in Switzerland, Kobe Bryant in Los Angeles, and Tinker Hatfield in Portland.