Scientists identify mutation that could facilitate H5N1 'bird flu' virus infection and potential transmission in humans

 Avian influenzaviruses typically require several mutations to adapt and spread among humans, but what happens when just one change can increase the risk of becoming a pandemic virus? A recent study led by scientists at Scripps Research reveals that a single mutation in the H5N1 "bird flu" virus that has recently infected dairy cows in the U.S. could enhance the virus' ability to attach to human cells, potentially increasing the risk of passing from person to person. The findings -- published in Science on December 5, 2024 -- highlight the need to monitor H5N1's evolution.

Currently, there are no documented cases of H5N1 transmitting between people: bird flu cases in humans have been linked to close contact with contaminated environments as well as infected birds (including poultry), dairy cows and other animals. However, public health officials are concerned about the potential for the virus to evolve to transmit efficiently between humans, which could lead to a new, potentially deadly pandemic.

The flu virus attaches to its host via a protein called hemagglutinin that binds to glycan receptors on the surfaces of host cells. Glycans are chains of sugar molecules on cell surface proteins that can act as binding sites for some viruses. Avian (bird) influenza viruses like H5N1 primarily infect hosts with sialic acid-containing glycan receptors found in birds (avian-type receptors). While the viruses rarely adapt to humans, if they evolve to recognize sialylated glycan receptors found in people (human-type receptors), they could gain the ability to infect and possibly transmit between humans.

"Monitoring changes in receptor specificity (the way a virus recognizes host cells) is crucial because receptor binding is a key step toward transmissibility," says Ian Wilson, DPhil, co-senior author and the Hansen Professor of Structural Biology at Scripps Research. "That being said, receptor mutations alone don't guarantee that the virus will transmit between humans."

Past cases in which avian viruses adapted to infect and transmit between people required multiple mutations, usually at least three. But for the H5N1 2.3.4.4b strain (A/Texas/37/2024) isolated from the first human infection with a bovine H5N1 virus in the United States, researchers found that just a single amino acid mutation in the hemagglutinin could switch specificity to binding human-type receptors. Here, bovine refers to the species for dairy cows that were the immediate source of the virus for the human infection. Importantly, the mutation wasn't introduced into the whole virus -- only the hemagglutinin protein to study its receptor-binding properties.

For their study, the research team introduced several mutations into the H5N1 2.3.4.4b hemagglutinin protein that had been involved in receptor specificity changes in previous avian viruses. These mutations were selected to mimic genetic changes that could occur naturally. When the team assessed the impact of one of these mutations, Q226L, on the virus' ability to bind to human-type receptors, they found that that mutation significantly improved how the virus attached to glycan receptors, which represent those found in human cells.

sources-science daily