A single mutation in the H5N1 avian flu virus can cause the virus to change its affinity from animal-type receptors to human-type receptors and increase the risk of triggering a future flu pandemic, according to a new study published this Thursday in the magazine Science.
Clade 2.3.4.4b of the highly pathogenic avian influenza virus H5N1 emerged in North America in 2021 and has demonstrated a remarkable ability to infect a wide range of hosts, including bird species, marine mammals, and humans. By 2024, this virus has spread widely among dairy cattle in the United States and has been detected on at least 282 farms in 14 states, in addition to leading to several confirmed human infections.
These new findings highlight the crucial need for continued surveillance of emerging H5N1 mutations, according to the researchers, as even subtle genetic changes could increase the virus’s ability to adapt and transmit to humans, potentially triggering a future pandemic. flu.
A couple of changes in the chain
For this new job, Ting-Hui Lin and his team engineered targeted mutations in the receptor binding site (RBS) of the first known bovine H5N1 virus to infect humans (A/Texas/37/2024, Texas). Next, through a series of experiments, the authors discovered that a single mutation in the HA protein can change its receptor preference entirely, increasing the virus’s potential for human transmission.
According to the study authors, the findings underscore the increased risk of interspecies transmission of H5N1, especially among those who work closely with livestock.
Additionally, the scientists found that adding a second mutation further improves binding to the human receptor to the near-pandemic levels seen in the 2009 H1N1 virus, while eliminating the affinity of the avian receptor.
A critical barrier
According to the study authors, the findings underscore the increased risk of interspecies transmission of H5N1, especially among those working closely with livestock or during co-infections with seasonal influenza, which could facilitate redistribution events.
Although there are currently no documented cases of human-to-human transmission of H5N1 bovine flu, the virus’ history of high mortality rates and its ability to adapt have raised serious concerns about a pandemic threat. A critical barrier to human-to-human transmission is the virus’s receptor binding preference, which currently favors avian receptors over human ones.
However, several influenza pandemics in the past illustrate that viral hemagglutinin (HA) proteins can acquire mutations that change receptor binding preference from animal-type receptors to human-type receptors.
“It has already happened in other pandemics”
“For a virus to acquire the ability to be transmitted between humans, it must overcome various barriers or climb multiple steps so that the virus ends up adapting to humans or other hosts,” he explains. Aitor Nogalesvirologist at the Animal Health Research Center (CISA-INIA-CSIC). One of these barriers is the virus’s ability to enter cells. “At the moment, the H5N1 virus isolated in cattle retains the preference for bird cells, but the change in tropism is not a rare event in influenza and has already occurred in other pandemics of this disease, including the last one in 2009.”
This type of change is not a rare occurrence in flu and has occurred in other flu pandemics, including the last one in 2009.
Aitor Nogales,
— Virologist at CISA-INIA-CSIC
In Nogales’ opinion, it is a change that we must monitor, along with other amino acid changes previously identified due to their possible consequences on the adaptation of the virus to other mammals or humans. “We must not forget that the flu virus has an unusual capacity for adaptation and evolution,” he warns. “And all flu pandemics have had avian flu as an essential actor in their origin.”
The first time it is demonstrated
Elisa Pérez Ramírez, virologist at CISA-INIA-CSIC, believes that the result is very relevant, because until now with other previous versions of the H5N1 virus it had been seen that at least three mutations were needed to achieve this change in specificity in the receptors. “It is the first time that it has been shown that a single mutation would be enough for these H5N1 viruses to find the key that fits our lock,” he points out. Even so, he points out, “it must be put in context because for this adaptation to occur the receivers would have to greatly improve their air transmission capacity.”
It is the first time that it has been shown that a single mutation would be enough for these H5N1 viruses to find the key that fits our lock.
Elisa Pérez Ramírez
— Virologist at CISA-INIA-CSIC
Angela Vazqueza researcher at the Severo Ochoa Molecular Biology Center (CBMSO), believes that it is very relevant that with a single mutation the virus can bind to the receptor that is in humans. “Yes, it is true that they say that in order for a pandemic to occur later, more mutations must occur,” he explains to elDiario.es. “One thing is that you can get infected and another is that you can transmit it, but once it is in people it is easier for those mutations to occur, that is, it is getting closer and closer.”
In the opinion of the expert, who is about to return to Antarctica to continue studying the spread of the virus among birds, these new data confirm that the situation is increasingly risky. “We are climbing steps towards the scenario in which the virus is more susceptible to infecting humans and that they can transmit it,” he summarizes.
We are climbing steps towards the scenario in which the virus is more susceptible to infecting humans and they can transmit it
Angela Vazquez
— Researcher at the Severo Ochoa Molecular Biology Center (CBMSO)
Iván Sanz MuñozScientific and Virological Surveillance Manager at the National Influenza Center of Valladolid, believes that this result is a real concern, but sees some nuances. “In the udders of cows there are avian receptors in a greater proportion than human receptors, so frequent selection of this mutation, and its becoming the majority, is unlikely,” he says. “This, along with other factors, have in fact been the limiting severity in most of the 57 cases detected so far in this country.”
Sanz Muñoz recalls that the authors themselves comment that this mutation alone implies a change, but this change only means a weak binding to human receptors, showing that the participation of other additional or accessory mutations is necessary for this to become truly a problem. “The issue is that we are one step closer to that point, and each mutation that the virus fixes is just one more step towards a possible pandemic,” he admits. “That’s why it’s vital that we control it through surveillance and other functions.”
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