A team of American scientists has discovered a single mutation that could facilitate the infection of the avian flu virus and its possible transmission to humans, a finding that demonstrates the importance of maintaining proactive surveillance of the evolution of the H5N1 and similar strains.
The details of the study, led by researchers from the Scripps Research Institute from San Diego, California, were published this Thursday in Science.
To attach to its host, the flu virus uses a protein (hemagglutinin) that binds to receptors on the surface of the host’s cells called glycan receptors.
The viruses of the bird flu like H5N1 primarily infect hosts with sialic acid-containing glycan receptors found in birds. Although viruses rarely adapt to humans, if they evolve to recognize these types of receptors in people, they could acquire the ability to infect and possibly transmit between humans.
However, “receptor mutations alone do not guarantee that the virus will be transmitted between humans,” he emphasizes. Ian Wilsonco-senior author and Hansen Professor of Structural Biology at Scripps Research.
Until now, when avian viruses have managed to infect and transmit between people, they have done so by adapting to bind to receptors with multiple mutations (at least three).
But in the case of the strain H5N1 2.3.4.4b (A/Texas/37/2024) isolated from the first human infection with a bovine H5N1 virus in the United States, researchers discovered that a single mutation in hemagglutinin could facilitate binding to human-like receptors.
In this case, in which dairy cows were the immediate source of the virus for human infection, the mutation was not introduced into the entire virus, but only into the hemagglutinin protein.
To study how this mutation happened, the team introduced several mutations into the H5N1 hemagglutinin 2.3.4.4b protein. These mutations were selected to mimic genetic changes that might occur naturally.
By evaluating the impact of one of these mutations, Q226L, on the virus’s ability to bind to human-like receptors, they found that this mutation significantly improved the way the virus bound to human-like receptors. glycan receptorswhich represent those found in human cells.
“The findings demonstrate the ease with which this virus could evolve to recognize human-type receptors,” says the first author, Ting-Hui Linpostdoctoral research associate at Scripps Research.
The team wanted to understand how natural mutations, such as Q226L, could arise and what their impact might be.
To investigate possible mutations that could allow H5N1 hemagglutinin 2.3.4.4b to bind to human receptors, the team used assays with the laboratory of co-senior author James Paulsonprofessor at Scripps Research.
Those assays, which mimicked the way a virus attaches to a cell, allowed researchers to precisely track how the altered H5N1 hemagglutinin interacted with human-like receptors.
“Our experiments revealed that the Q226L mutation could significantly increase the virus’s ability to target and adhere to human-like receptors. “This mutation gives the virus a foothold in human cells that it did not have before, so this finding is a warning signal for a possible adaptation to people,” explains Paulson.
However, the change alone may not be enough to allow transmission between humans. Others would probably be necessary genetic changes for the virus to spread effectively between people, the authors emphasize.
But given the increasing number of human cases of H5N1 resulting from direct contact with infected animalsthe results highlight the need for proactive monitoring of the evolution of H5N1 and similar strains of avian influenza.
“This type of research helps us understand what mutations to watch for and how to respond appropriately,” Wilson concludes.
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