Bird flu outbreaks in humans may remain rare thanks to this gene

Researchers from the United Kingdom have found that a human gene plays a crucial role in preventing the avian flu from replicating in people.

The study, published Wednesday in Nature, found the gene called BTN3A3 helps prevent the spread of the avian flu among humans, offering a potential reason why many people have never contracted the disease.

“This gene had already been identified before but the discovery of this gene being antiviral against avian flu is a novelty,” Rute Pinto, co-author of the study and a scientist at the Roslin Institute at the University of Edinburgh, told Global News.

“It was a ‘yes moment’… BTN3A3 was inhibiting avian strains but not human strains, that was the first discovery,” she said.

Avian influenza, also known as bird flu, mainly spreads among wild birds such as ducks and gulls and can also infect farmed birds and domestic poultry such as chicken, turkey and quail.

The current outbreak circulating North and South America is known as H5N1 clade 2.3.4.4b. It has killed record numbers of birds and infected mammals such as skunks, minks and sea lions.

Although rare, the virus can sometimes spread from bird to human, as was the recent case in Cambodia, where an 11-year-old girl, who lived near a conservation area, reportedly died from the virus.

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To unravel the mystery behind the transmission of viruses from animals to humans, the team of scientists from the MRC-University of Glasgow Centre for Virus Research led a four-year study. They looked at more than 800 human genes and compared them during infection with seasonal viruses or the avian flu.

While scientists already knew about the existence of the BTN3A3 gene in all humans, the researchers were not aware that it helped protect against the bird flu. They found the gene was a powerful barrier for bird flu but not for human viruses, like seasonal influenza.

This gene is predominantly found in the spleen, lungs and upper respiratory tract, Pinto said.

“This is important because the flu is a respiratory virus. So it makes sense that BTN3A3 is present where the virus would normally infect,” she added.

The antiviral activity of the gene evolved around 40 million years ago, Pinto said. It developed in mammals, primarily in monkeys, gorillas and of course, humans. But the gene tends not to exist in avian species, Pinto said.

Although human cases of avian flu remain rare, Shayan Sharif, a professor and associate dean with the Ontario Veterinary College at the University of Guelph, warned the virus has the potential to become a human threat.

“One of the big things about avian influenza viruses is that it usually can’t bind very strongly to the receptors that we have in our respiratory system,” he said. “Our saving grace is the fact that we don’t provide and nurturing environment for avian influenza viruses.”

But that can change if the virus decide to mutate and adapt.

They can evade genes like BTN3A3, and already have, Sharif said, adding that this is why studies like the one from the University of Glasgow are “critical.”

“If you start swabbing, for example, birds or mammals to identify their viruses and then determine whether or not those viruses have the mutation that would render them resistant to human genes, then we can predict that any of those viruses would be able to replicate in humans,” he said.

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Pinto agreed.

Viruses, like the bird flu, can easily mutate and become resistant around antiviral genes, like BTN3A3, she said.

But, for example, if a virus is spreading around a poultry farm, within days or even within hours, you can sequence it.

“You can then very easily go through the sequence of the virus and say, ‘Look, maybe this virus has BTN3A3 bypassing mutations,'” she said. “Then you can reinforce the health and safety measurements for the people that deal with these viruses … like vets and farmers.”

Although this one gene was found to have antiviral properties, Sharif said the human body has many more of these defence mechanisms.

“There are a lot of other genes that determine resistance to these sorts of zoonotic pathogens, and this is one of those,” he said.

But, he said, BTN3A3 is part of a larger arsenal of weapons against all influenza viruses.

Emphasizing the significance of such studies, he said that despite the current “peacetime” phase of the avian flu, there remains a possibility of resurgence, particularly during the upcoming fall or winter season.

According to Environment Canada data, there has been an overall downward trend of confirmed avian flu cases across the country since late January.

“I don’t really think that there’s any assurance that the virus is not going to come back. But our hope is that the virus is not going to be affecting us all that much during the fall season,” Sharif said.

“But from my understanding, the virus is not quite done yet.”

— with files from Reuters