The genetic sequence of the H5N1 bird flu virus that infected a teenager in British Columbia shows that the virus had undergone mutational changes that would make it easier for that version of H5N1 to infect humans, say scientists who studied the data.
There is currently no evidence that the teenager, who is in critical condition in hospital, has infected anyone else. If so, it’s likely that this mutated version of the virus will die out when the teen’s illness disappears. The source of the teen’s infection has not yet been determined, so it is impossible to know for sure whether the mutations were in the virus that infected him or her. But scientists think it’s more likely that the mutations developed over the course of his or her infection.
Still, the fact that the mutations occurred at all is a reminder that H5N1 is a dangerous virus for humans, one that could potentially cause a pandemic if it acquired the ability to easily infect humans, flu virologists say.
“This is by no means Day 1 of a pandemic. There’s no evidence… of human-to-human spread, and that’s all good. But this is exactly the scenario we fear,” Scott Hensley, professor of microbiology at the University of Pennsylvania Perelman School of Medicine, told STAT in an interview.
Hensley sparked some concern on social media platforms last weekend when he noted that the genetic sequence of the virus showed significant mutational changes in the hemagglutinin, a protein on the surface of the virus that attaches to cells the virus is trying to invade. The sequence data have been placed in open-access databases by the Public Health Agency of Canada.
“This is bad news,” Hensley said in an interview Bluesky Post on Saturday. “We must monitor this situation closely and increase our surveillance efforts.”
H5N1’s hemagglutinin preferentially binds to cells with receptors known as alpha 2-3, which are abundant in wild birds and domestic poultry, but also found in the conjunctiva, the tissue surrounding the human eyes, and in the upper respiratory tract of man. The cell receptors in the human lungs are known as alpha 2-6. It is thought that in order to become a virus that can spread easily among humans, H5N1 must acquire the ability to attach to this latter type of receptor.
Two mutations in the Canadian teen virus are known to help flu viruses make this attachment switch. “Both sites play an important role in … binding specificity,” said Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Center in Seattle, in a series of messages respond to Hensley.
Hensley agreed. “Ten out of ten flu virologists will tell you that these substitutions are important for effective receptor specificity. There is no doubt about that.”
The British Columbia case has received significant attention for two reasons. First, it remains a mystery how the teenager became infected. Second, while H5N1 cases have historically been found to cause severe illness (and death) in a significant number of cases, the versions of the virus currently circulating in North America have caused only mild infections, except in this case.
The United States reported this on Monday 53 confirmed infections This year, all but one involved dairy farm workers or people involved in culling infected poultry farms. All of these people experienced mild illness, usually conjunctivitis (pink eye) and in some cases mild respiratory symptoms. None of the infected people in the US were sick enough to be hospitalized.
The British Columbia teen was admitted to hospital on Nov. 8 and remains in critical condition, provincial health officer Bonnie Henry said in an email on Monday. It appears that the individual did not transmit the infection to anyone else.
“All contacts [are] … now more than 10 days after exposure,” Henry said, identifying people who were in contact with the teen before the illness and putting transmission precautions in place outside the incubation period for flu.
The version of the virus that infected the teen is not the version circulating among dairy cattle in the US. Both come from an H5N1 strain known as 2.3.4.4b. But the cow virus comes from a subset of viruses known as genotype B3.13. The teenager was infected with a virus of the D1.1 genotype – a version of the virus circulating among wild birds. It is the version of the virus responsible for a number of poultry farm outbreaks in both British Columbia and Washington state, where 11 confirmed and three probable cases of H5N1 infection have been discovered in the past month.
Richard Webby, an influenza virologist and director of the World Health Organization’s Collaborating Center for Studies on the Ecology of Influenza in Animals, based at St. Jude Children’s Research Hospital in Memphis, Tennessee, said he finds the D1.1 viruses particularly concerning .
Influenza A viruses have the ability to swap genes, and this version of H5N1 picked up a different neuraminidase gene (the N in the name of a flu virus) than the B3.13 viruses, Webby said. Sometimes that kind of change can prompt the virus to make adjustments (mutations) to the hemagglutinin in response to the change.
“Just because it picked up the new thing [neuraminidase] does not necessarily mean the [hemagglutinin] will change,” Webby said in an email. “But the old combination was clearly well coordinated. The new one [neuraminidase] could change that balance and help promote change, but that’s a could instead of one shall.”
Hensley said the evidence that the virus is changing in the teenager should serve as a reminder that the mild cases the U.S. has recorded this year may not reflect how the virus would behave if it started spreading among people. He is unsettled by the sheer scale of the virus in the environment, and people’s daily exposure to it, on infected dairy or poultry farms.
“You have a lot of potential human exposures and then what you fear is a random substitution that arises during that infection that gives the virus a favorable profile to infect … transmission among humans, and then that starts to take off. That is the fear,” he said.
“There’s no indication that that second part happened here,” Hensley said, referring to the British Columbia case. “But it makes me nervous, number 1, to see these replacements coming out and number 2, to see the replacements associated with what appears to be such a serious case.”