Bird flu risk to humans: Canadian case has unsettling viral mutations

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 people, scientists who have studied the data say. 

There’s currently no evidence the teenager, who remains in critical condition in hospital, infected anyone else. If that’s the case, it is likely this mutated version of the virus would die out when the teen’s illness resolves. The source of the teen’s infection has not been determined, so it’s impossible to know for sure if the mutations were in the virus that infected him or her. But scientists think it is more likely that the mutations developed during 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 people, one that could potentially trigger a pandemic if it acquired the capacity to easily infect people, flu virologists say.

“By no means is this Day 1 of a pandemic. There’s no indication … of human-to-human spread, which is all good. But this is exactly the scenario that we fear,” Scott Hensley, a professor of microbiology at the University of Pennsylvania’s Perelman School of Medicine, told STAT in an interview.

Hensley sparked some concern on social media platforms over the weekend when he remarked on the fact that the genetic sequence of the virus showed key mutational changes in the hemagglutinin, a protein on the virus’ surface that attaches to cells the virus is trying to invade. The sequence data were posted to open-access databases by the Public Health Agency of Canada. 

“This is bad news,” Hensley said in a Bluesky post on Saturday. “We need to closely monitor this situation 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 are also found in the conjunctiva, the tissue surrounding human eyes, and in human upper airways. The cell receptors in human lungs are known as alpha 2-6. It’s thought that to become a virus capable of spreading easily among people, H5N1 would need to acquire the ability to attach to this latter type of receptor.

Two mutations spotted in the Canadian teen’s virus are known to help flu viruses make this attachment switch. “Both these sites play an important role in … binding specificity,” Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Center in Seattle, said in a series of posts responding to Hensley. 

Hensley agreed. “Ten out of 10 flu virologists will tell you that these substitutions are important for effective receptor specificity. There’s no question about that.”

The British Columbia case is garnering substantial attention for two reasons. Firstly, how the teenager became infected remains a mystery. Secondly, while H5N1 cases have historically been seen to cause severe disease — and death — in a substantial number of cases, the versions of the virus currently circulating in North America have triggered only mild infections except for in this case. 

As of Monday, the United States had reported 53 confirmed infections this year, all but one of which were in dairy farmworkers or people involved in culling infected poultry operations. All of these people experienced mild illness, mostly conjunctivitis — pink eye — and in some cases minor respiratory symptoms. None of the people infected in the U.S. was ill enough to require hospitalization.

The British Columbia teen was admitted to hospital on Nov. 8 and remains in critical condition there, Provincial Health Officer Bonnie Henry said in an email Monday. It does appear that the individual did not transmit the infection to anyone else.

“All contacts [are] … now beyond 10 days post exposure,” Henry said, which would put people who were in contact with the teen before the illness was identified and transmission precautions were put in place outside of the incubation period for flu.

The version of the virus that infected the teenager is not the one circulating in dairy cattle in the U.S. Both are from a strain of H5N1 known as 2.3.4.4b. But the cow virus is from a subset of viruses known as genotype B3.13. The teen was infected with a virus from the D1.1 genotype — a version of the virus circulating in wild birds. It is the version of the virus responsible for a number of poultry operation outbreaks, both in British Columbia and in Washington state, where 11 confirmed and three probable cases of H5N1 infection have been detected in the past month or so.

Richard Webby, a flu virologist and director of the World Health Organization’s Collaborating Center for Studies on the Ecology of Influenza in Animals, located at St. Jude Children’s Research Hospital in Memphis, Tenn., said he finds the D1.1 viruses particularly concerning.

Influenza A viruses have the capacity to swap genes, and this version of H5N1 has picked up a different neuraminidase gene (the N in a flu virus’ name) than the B3.13 viruses have, Webby said. Sometimes that type of change can push the virus to make adaptations — mutations — in the hemagglutinin in response to the change. 

“Just because it has picked up the new [neuraminidase] doesn’t necessarily mean the [hemagglutinin] will change,” Webby said in an email. “But the old combination was clearly well matched. The new [neuraminidase] could change that balance and help foster changes, but that is a could rather than a will.”

Hensley said the evidence of the virus 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 might behave if it were to start to spread in people. He is unsettled by the sheer volume of the virus in the environment, and the daily exposure of people to it, on infected dairy or poultry farms.

“You have a lot of potential human exposures and then what you fear is either a random substitution that emerges during that infection that gives the virus a favorable profile for infecting … transmitting among humans, and then that takes off. That’s the fear,” he said.

“There’s no indication that that second part has happened here,” Hensley said, referring to the British Columbia case. “But it makes me nervous, number 1, to see these substitutions emerge and number 2, to have the substitutions associated with what appears to be such a severe case.”