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A biosecurity warning sign is seen on a locked gate at a commercial poultry farm in Abbotsford, B.C., in November, 2024.DARRYL DYCK/The Canadian Press
University of British Columbia researchers say the unusual genetic mutations identified in Canada’s first human avian influenza case weakened the virus’ ability to bind to human cells, a critical first step in infection.
The findings were published in a study on Monday in Nature Communications. The authors said they conducted the research to explore whether the mutations signalled that avian flu was evolving to become better at infecting people, which was the prevailing assumption until this publication.
Senior author Sriram Subramaniam, a UBC professor of biochemistry and molecular biology, said he was surprised to learn the answer was no.
“We tested it exhaustively and, actually, it is really lousy at attaching to our human cells,” Dr. Subramaniam said in an interview. “The bottom line is that we should be looking at the functional effects of these mutations, and not just tracking the sequence changes alone.”
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A B.C. teen from the Fraser Valley, who fell ill two years ago, was the first and remains the only person known to have contracted avian flu in Canada. The young girl was discharged from hospital in January, 2025, after spending roughly two months in critical condition. The source of the case may never be officially identified.
Scientists, at that time, identified three genetic mutations in the B.C. case that raised global concern. The new research focused on two of those mutations that were found in spike proteins, which act like a door for viruses to enter healthy human cells.
A similar mutation was detected in samples from a Louisiana patient whose death was announced in January last year. This was the first of two avian flu deaths that have been recorded in the United States.
Avian flu, also known as bird flu, is a contagious viral infection that most often turns up in wild and farmed birds. The virus is so contagious and severe in birds that more than 17.5 million, mostly chicken and turkeys, have died or been killed under orders from the Canadian Food Inspection Agency since 2022.
Human-to-human transmission of avian flu is exceedingly rare and there is no evidence of sustained spread among people. The version of this virus circulating in Canada is an H5N1 strain.
The UBC team used a series of tests to better understand the mutations, including by using cryo-electron microscopes to map their structures at near atomic detail. Dr. Subramaniam said the experiments showed that the mutations weakened receptor binding.
Viruses typically attach to cells within the upper respiratory tract but that did not happen with these mutations. However, he said that testing indicated that the virus could have infected cells lower down, which led to the severe illness in the B.C. patient.
“We don’t have proof that’s exactly what happened, but we think that the upper respiratory tract didn’t do the normal job of snagging the virus and letting it in,” he said. “There’s lots of complex factors, lots of interactions, and eventually we show that it had some capability to infect cells.”
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The study found that the virus, after attaching to a cell, must fuse with the cell membrane. This allows its genetic material to enter the cell, where it can be replicated.
In human lung cells, the researchers found that the mutated protein could trigger this fusion despite its weak receptor binding, but it was far less efficient than with other H5N1 strains.
“Eventually, that let it gain some entry and that probably led to the effects that we saw in the individual,” Dr. Subramaniam explained.
The research underscores the need to learn more about how an animal virus is able to infect people, he said. A greater understanding will help scientists and public health officials better assess and respond to threats in the future.
“There’s a lot more to do,” Dr. Subramaniam said. “But the good news is that we’ve not seen evidence that the virus became better adapted to infecting human cells.”