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The H5N1 avian influenza virus is one mutation away from becoming infectious to humans, enabling it to spread from one person to another, scientists have revealed.
Researchers from Scripps Research have identified a mutation sourced from an infected dairy cow in the US state of Texas which could enable the spread of viral infection among humans.
Their findings, published in the journal Science, underline the potential risk of the virus towards triggering another pandemic.
There are no cases of human-to-human H5N1 transmissions currently, but those of animal-to-human infection have been increasing this year. The H5N1 strain clade 2.3.4.4b — detected in North America since 2021 — has been widely spreading among poultry, wild birds, mammals and marine species, leading to a global epizootic event.
Outbreaks in 718 dairy herds from 15 US states have been reported until December 5, according to the US-based Centers for Disease Control and Prevention (CDC). As many as 58 humans have been infected after being exposed to dairy cattle and poultry in the US.
Current risk to humans is low, according to the CDC. However, the scientific community is concerned about the virus evolving and efficiently adapting to humans, leading to a potential pandemic. The World Health Organization (WHO) has estimated that bird flu has 52 per cent chances of fatality.
The world health agency has also urged stepping up surveillance among poultry and wild birds.
“The flu virus attaches to its host via a protein called hemagglutinin that binds to glycan receptors on the surfaces of host cells,” a statement issued by the researchers said.
Glycans are chains of sugar molecules on cell surface proteins that can act as binding sites for some viruses, they said.
Viruses such as H5N1 infect hosts mainly with sialic acid which contains glycan receptors present in birds. Though viruses rarely adapt to humans, they can evolve to identify sialylated glycan (human-type) receptors found in humans and can thereby succeed in their ability to infect humans and spread between them.
These receptors are abundantly expressed in the upper human airway, the study noted.
Another concern the scientists shared is that earlier, the avian virus which adapted to infect and transmit among humans required at least three mutations. But the H5N1 2.3.4.4b strain sourced from the first human to be infected from a cow in Texas showed that a single amino acid mutation in the hemagglutinin could boost its ability to bind to human-type receptors.
Interestingly, the mutation was not specific to the whole virus but was limited to the hemagglutinin protein.
The scientists introduced multiple mutations to the H5N1 2.3.4.4b clade. The deliberate mutations were introduced to assess the naturally occurring genetic changes the virus may undergo to increase adaptability in binding with human-type receptors.
The results revealed that a specific mutation, ‘Gln226Leu substitution’ or Q226L, significantly improved its ability to attach the glycan receptors found in humans.
“Our experiments revealed that the Q226L mutation could significantly increase the virus’ ability to target and attach to human-type receptors,” explained co-author James Paulson.
This mutation gives the virus a foothold on human cells that it didn’t have before, which is why this finding is a red flag for possible adaptation to people, he added.
The study stated that a second mutation, Asn224Lys, gave a better hold to the virus.
“The findings demonstrate how easily this virus could evolve to recognise human-type receptors,” said the first author and a postdoctoral associate at Scripps Research, Ting-Hui Lin.
“A switch in receptor binding preference of human viruses from avian or swine virus progenitors was previously shown for influenza pandemics in 1918, 1957, 1968, and 2009,” the study pointed out.
It also observed that the mutation in question was tested by scientists in a duck and a few humans during the 2010 H5N1 outbreak in Egypt. But it did not demonstrate the virus affecting human receptor binding, unlike now.
Paulson added that their study does not suggest that such an evolution has occurred or that the current H5N1 virus with only this mutation would be transmissible between humans.
He told LiveScience that a high concentration of viral material from cattle, poultry and infected animals is responsible for the infection recorded in humans so far.
The ability to bind to human receptors alone may not be enough to succeed in human-to-human spread, the researchers noted. Other genetic changes — such as mutations in polymerase basic 2 (E627K) — that enable viral replication and bring stability in human cells would probably be necessary for the virus to spread efficiently among humans.
However, researchers who were not part of the study have already highlighted their concerns observed in other cases. A recent study revealed that the mutation PB2-E627K found in Texas showed an increased ability to transmit between ferrets, when exposed via air in an experiment.
Also, the mutation found in a teenager from the Canadian province of British Columbia was similar to Q226L in that both could attach to the glycan receptors found in humans.
The development left scientists feeling concerned.
Scott Hensley, a professor at Penn Institute of Immunology explained on social media platform Bluesky that the hemagglutinin that primarily binds to bird cell receptors was found to infect equivalent receptors in the tissues located in human eyes, the upper respiratory tract and conjunctiva.
The Gln226Leu mutation has previously been flagged in other studies of H5N1, which also indicated the virus’s ability to infect humans.
