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In December 2024, a paper in Science caught widespread attention when it proposed that a single mutation in the H5N1 avian flu virus could potentially allow it to infect humans. While the study was groundbreaking in its insights, some media outlets took the findings a step too far, suggesting that we may be “one mutation away” from an H5N1 pandemic. However, experts warn that the situation is not as dire as some have made it out to be.
A Step-by-Step Process, Not a Single Leap
H5N1, commonly known as bird flu, has been circulating among animals for years, especially in birds and, more recently, in cattle. As of now, there are no documented cases of human-to-human transmission. One of the critical barriers preventing this is the virus’s inability to bind to human receptors in the respiratory tract—a necessary step for it to spread between people.
In the study, researchers introduced a mutation in the hemagglutinin (HA) protein of the H5N1 virus. This mutation allowed the virus to bind to human receptors in the lab. While this finding is important, it does not mean that the virus is on the cusp of triggering a pandemic. A virus would need multiple additional adaptations to effectively spread among humans.
The Mutation Explained
The H5N1 virus primarily binds to receptors in birds, which contain α2-3 sialic acid. In contrast, human influenza viruses bind to α2-6 sialic acid receptors found in the human upper respiratory tract. For H5N1 to spread to humans, it would need to evolve the ability to attach to these human-specific receptors.
The study found that a single mutation at residue 226 of the virus’s hemagglutinin protein (a change from glutamine to leucine) allowed it to bind to human receptors in laboratory settings. However, the virus would also need further mutations to enhance its transmissibility and its ability to enter and replicate in human cells—steps that are far from guaranteed.
A Pandemic in the Animal World
H5N1 has already created a panzootic—an epidemic of animal diseases that spans multiple species and continents. The virus has infected hundreds of species, including wild birds, poultry, and mammals, including cows, in the United States. Dairy cows became an unexpected reservoir for the virus in 2024, and the virus has been detected on over 900 dairy farms.
Despite its wide spread among animals, H5N1 has not caused sustained human-to-human transmission. As of late 2024, there have been over 900 documented human cases, but most of these were linked to direct contact with infected poultry or animals. Notably, recent cases among dairy farm workers have mostly resulted in mild illnesses, with no fatalities or evidence of person-to-person transmission.
Why the Virus Isn’t a Threat—Yet
The primary reason why H5N1 isn’t on the brink of becoming a pandemic is that the virus has yet to acquire the right combination of mutations that would allow it to efficiently spread among humans. This would require not only binding to human receptors but also overcoming our immune defenses and finding a way to spread easily through the air.
Researchers have found no mutations in H5N1’s hemagglutinin gene that would significantly increase its infectiousness or ability to transmit between humans. Even if a mutation were to improve the virus’s ability to infect humans, it could have other detrimental effects on the virus’s survival, ultimately making it less effective.
Vigilance and Preparation
While the risk to the general public is still low, experts stress the importance of ongoing surveillance and prevention efforts. The influenza virus is highly adaptable, and continued global circulation of H5N1 in animals makes it crucial to improve biosecurity measures in farming, enhance veterinary surveillance, and promote the One Health approach—a collaborative effort between human and animal health sectors.
Public health efforts should focus on protecting workers exposed to infected animals and investigating each human case thoroughly to detect any signs of increased virulence. In addition, research into universal vaccines and new therapeutic strategies remains essential.
In conclusion, while we are not “one mutation away” from a pandemic, the risk is not to be ignored. Vigilance, research, and collaboration remain our best defenses against a potential H5N1 threat.
