H5N1 bird flu is closer to gaining pandemic potential than we thought

The H5N1 avian influenza virus that has spread globally is more capable of infecting humans than earlier strains. What’s more, a single mutation can allow it to infect cells in our noses and throats, making it more likely to spread through the air.

This change alone is not enough for the virus to cause a pandemic. However, if a virus with this mutation swapped genes with a human influenza virus, it could gain pandemic potential almost immediately.

“The more people that are infected, the more likely it is that something like this will happen.” Ian Wilson at Scripps Research Institute in California. Still, Wilson believes the risk remains low.

H5N1 avian influenza emerged in the 1990s, possibly in poultry in China, and spread globally. Around 2020, new variants of the virus emerged and spread more widely, reaching the Americas and Antarctica. It has infected poultry in large numbers and is also circulating among dairy cows in the United States, causing occasional human cases.

leadership team Debbie van Riel Researchers at Erasmus University Medical Center in the Netherlands have now infected human nose and throat cells with H5N1 variants from 2005 to 2022. They showed for the first time that the 2022 variant was better able to bind to these cells and replicate better within them. “That’s bad news,” Van Riel said.

“I don’t think the likelihood of this virus becoming a pandemic is very high,” she said. But the fact that the virus is better at infecting humans would give it more opportunities to acquire additional mutations, increasing its pandemic potential.

Meanwhile, Wilson and his colleagues have been studying the influenza virus’s key hemagglutinin protein. This protein binds to receptors on the outside of cells and determines which cells the virus can infect. Because it protrudes from the virus, it is also a major target of the immune system.

Currently, the H5N1 hemagglutinin binds primarily to receptors deep in the human lungs. This means it can cause serious illness but is unlikely to pass out of the body and infect others. To do this, the virus needs to infect cells in the lining of the nose and throat, which means the virus can be expelled through coughing or sneezing and infect other people.

Van Riel’s research suggests that the virus can do this to some extent, but it’s unclear whether the virus binds to the primary receptor on these cells. It was thought that H5N1 required multiple mutations to bind strongly to these receptors, but Wilson’s team now shows that with the current H5N1 variant, only one mutation is needed.

Team members say this change alone won’t make the virus pandemic-capable Jim Paulsonalso at The Scripps Research Institute. “We believe this property is necessary for pandemic virus transmission, but importantly not sufficient,” he said.

Paulson said other changes are needed for the virus to start replicating and spreading from person to person, but those changes are not yet known. “There’s a lot of biology we don’t even know about,” he said.

However, once an H5N1 virus that infects humans acquires a receptor-switching mutation, it has the opportunity to evolve these other changes.

What’s more, it could theoretically gain all the abilities it needs in one fell swoop by exchanging genes with a human virus that infects the same individual. Previous influenza pandemics have been caused by animal and human influenza viruses exchanging genes, Paulson said.

“It’s very concerning,” said Aris Kazorakis Professor at the University of Oxford, who was not involved in either study. “Every time a virus jumps into humans, it’s a dice roll for the virus.”

How deadly is the H5N1 influenza pandemic?

If H5N1 bird flu does start spreading from person to person, the big question is how deadly it will be. Since 2003, half of those diagnosed with the virus have died. However, the true infection fatality rate is likely to be lower because many cases may go undetected and milder cases are more likely to be missed.

Since the dairy outbreak began, about 60 people have been infected in the United States, almost all of whom had only mild symptoms. Why not understoodbut one explanation is that many people get the infection through their eyes. “This is known to produce much milder results,” Kazorakis said.

It’s also thought that viruses become less dangerous when they switch from binding to receptors deep in the lungs to receptors higher in the respiratory tract. But puzzling aspects of the U.S. cases left Paulson unsure whether the same applies to H5N1. “To be honest, I don’t know what to think right now,” he said.

“I don’t think there’s any reason to be complacent on this and if this virus spreads easily from person to person, expect a ‘mild’ situation,” Kazulakis said.

Wilson’s team studied the hemagglutinin protein alone, so there was no way the mutant protein could have leaked in the lab. “No viruses are used here at all,” he said.