New pandemic in sight? A study published this week reveals that a single point change in the H5N1 virus, which infects dairy cows, could allow it to bind to receptors on human cells, raising concerns that it could more easily transmit to humans.
A team of researchers has found that , the highly pathogenic strain of bird flu virus currently spreading in U.S. dairy cows, just needs more a single mutation to easily attach to human cells found in the upper respiratory tract.
The conclusions of the , published this Thursday in the magazine Science, illustrate the potential path, with just one stepwhich the virus has to go through to become effective in human transmission – and can have important implications for a new pandemicif this mutation becomes widespread in nature.
Bird flu viruses are endowed with surface proteins that allow them to bind to receptors on bird cells, which allows the virus to enter the cells.
Bird cell receptors are different from those of humansbut this variation is “very subtle”, he says James Paulsonco-author of the study and biochemist at Scripps Research, cited by .
“For a new pandemic virus H5N1we know that the specificity of the receptors must be changed from an avian type to a human type”, he adds.
“So, what does it take?” the study authors sought to determine. And to the surprise of the researcher and his co-authors, this change only required a genetic change.
O specific group, or clade, of H5N1 responsible for the current outbreak was first detected in North America in 2021 and has affected a wide range of animal populations, including wild birds, bears, foxesa variety of marine mammals and, more recently, dairy cows.
Since in US dairy herds in the spring of this year, human cases have been linked mainly to birds or sick cows, and the Most human infections have been mild — among agricultural workers at high risk of exposure.
There are so far no signs of transmission between people — and the preference for binding to the virus receptor is a fundamental barrier for that.
“It’s obviously speculative, but if the virus binds better to human recipients, this is not good, because it will probably lead to human-to-human transmission”, says Jenna Guthmilleran immunologist at the University of Colorado Anschutz Medical Campus, who was not involved in the new investigation.
The study authors focused on altering one of H5N1’s surface proteins, the hemaglutininawhich contains the binding site that allows the virus to attach to host cell receptors and initiate infection.
The researchers generated viral proteins from genetic sequences of the virus isolated from the first human case in Texas, which occurred in a person who developed bird flu after exposure to an infected cow. No live virus was used in the experiment.
Afterwards, scientists created a series of mutations different amino acids in the hemagglutinin chain, or protein building blocks.
A single mutation that changed the 226th amino acid in the sequence on the other hand, it allowed H5N1 to change its binding affinity from receptors on bird cells to receptors on human cells in the upper respiratory tract.
A previous one, published in 2000 in Journal of Virologyshowed that several flu mutationsincluding those tested in the new paper, are important in binding to human receptors, says Guthmiller.
These genetic changes have been detected in previous subtypes of the flu virus that caused human pandemicslike those of 1918 and 2009.
But previous viruses required at least two mutations to be able to change their preference for human receptors, explains the co-author Ian Wilsonstructural and computational biologist at Scripps.
“This was surprising. It was just this single mutation which was enough to change the specificity of the receptor”, says Wilson.
Paulson adds that the specific mutation the scientists tested in the new study had already been investigated during H5N1 outbreaks in poultry and some humans in 2010, but did not affect virus binding to the human recipient.
“But the virus has subtly changed“, says Paulson. “Now this mutation causes the change.”
Wilson and Paulson note that the H5N1 protein mutated in their study binds weakly to human receptors, but more strongly than the H1N1 virus 2009, which caused the human “swine flu” pandemic.
“The initial infection is what worries us about starting a pandemicand we believe that the weak binding we see with this single mutation is at least equivalent to a known human pandemic virus“, says Paulson.
Guthmiller is not surprised by the findings, given the known importance of the 226 mutation in flu receptor preference, but concludes that “It’s never good when you see that all it takes is a mutation“.
