The H5N1 avian influenza virus is closer to gaining pandemic potential than we thought

The H5N1 bird flu virus that has spread around the world is already better at infecting humans than previous strains. What’s more, a single mutation could allow the virus to infect the cells lining our noses and throats, making it more likely to be transmitted through the air.

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

“The more people are infected, the more likely it is that something like this will arise,” he says. Ian Wilson At the Scripps Research Institute in California. Despite this, Wilson believes the risk is still low.

A particularly virulent form of the H5N1 avian influenza virus evolved in the 1990s, possibly in poultry in China, and has spread around the world. Around 2020, a new type of this virus emerged and spread more widely, reaching the Americas and Antarctica. The disease has infected domestic poultry in large numbers, and is also widespread among dairy cows in the United States, sometimes causing human cases.

Led team Debbie van Riel At Erasmus University Medical Center in the Netherlands, it has now infected human nose and throat cells with H5N1 variants from 2005 and 2022. They have shown for the first time that the 2022 variant is better at attaching to these cells and also better at replicating within them. . “It’s bad news,” Van Riel says.

“I don’t think the chances of the virus turning into a pandemic are very high,” she says. But the fact that the virus is better at infecting humans will give it more opportunities to acquire additional mutations that increase its ability to spread epidemically.

Meanwhile, Wilson and his colleagues were studying the important hemagglutinin protein of the influenza virus. This protein binds to receptors located on the outside of cells, which determines which cells the virus can infect. Because it emerges from the virus, it is also a prime target for the immune system.

At present, H5N1 hemagglutinin primarily binds to receptors found in humans deep in the lungs. This means it can cause severe illness but is unlikely to exit the body and infect others. To do this, the virus needs to infect the cells lining the nose and throat, which means viruses can be coughed or sneezed to infect others.

Van Riel’s study suggests that the virus can do this to some extent, but it is not clear whether the virus binds to key receptors on these cells. It was thought that multiple mutations would be needed for the H5N1 virus to bind strongly to these receptors, but Wilson’s team has now shown that with the current variant of the H5N1 virus, all it takes is a single mutation.

The team member says this change alone will not lead to a virus capable of becoming a pandemic Jim Paulsonand also at the Scripps Research Institute. “We view this property as required – but more importantly not sufficient – ​​for pandemic virus transmission,” he says.

Paulson says other changes are also necessary for the virus to begin replicating and spreading from person to person, and these changes are not well understood. “There’s a lot of biology we don’t even know,” he says.

However, once the human H5N1 virus acquires the receptor-switching mutation, it will have a chance to develop these other changes as well.

Furthermore, in theory, he could gain all the abilities he needed in one fell swoop by swapping genes with a human virus that infects the same individual. Paulson says many previous influenza pandemics were caused by the exchange of genes of animal and human influenza viruses.

“This is very worrying,” he says. Aris Katzourakis at the University of Oxford, who was not involved in either study. “Every transmission to humans gives the virus a roll of the dice.”

How serious is the H5N1 pandemic?

If H5N1 bird flu can start spreading from person to person, the big question is how deadly it will be. Of the people confirmed to be infected with the virus since 2003, half have died. However, the true death rate of infection could be lower because many cases may have gone undetected, and milder cases are likely to be missed.

Of the 60 or so people infected in the United States since the dairy outbreak began, almost all have shown only mild symptoms. Why Not understoodBut one explanation is that many became infected through the eyes. “This is known to have much milder outcomes,” says Katzorakis.

It is also believed that when viruses switch from binding to receptors deep in the lungs to receptors in the respiratory system, they become less dangerous. But the puzzling aspects of the cases in the United States made Paulson unsure that this would apply to H5N1. “Now, I don’t know what to think, to be honest,” he says.

“I don’t think there’s any reason to be complacent in this regard and expect ‘moderation’ if this virus becomes easily transmissible from human to human,” Katsourakis says.

Wilson’s team studied the hemagglutinin protein in isolation, so there was no chance of the mutant protein leaking into the laboratory. “There was no virus used at all here,” he says.

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