H5N1 bird flu poses a greater pandemic risk than anticipated

The H5N1 avian influenza virus that is circulating around the world is already more contagious than earlier strains. In addition, the single mutation allows it to infect cells lining the nose and throat, making it more likely to be transmitted through the air.

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

“The more people are infected, the more likely this is to happen,” he says. Ian Wilson At the Scripps Research Institute in California. Despite this, Wilson believes the risk remains low.

A particularly virulent strain of avian influenza, H5N1, originated in the 1990s, probably in domestic birds in China, and spread around the world. Around 2020, a new variant of the virus emerged and spread even more widely, reaching as far as the Americas and Antarctica. In the United States, poultry is infected in large numbers, dairy cattle are also infected, and occasionally humans are infected.

team led by Debbie Van Riel Researchers at Erasmus University Medical Center in the Netherlands infected cells in human noses and throats with the 2005 and 2022 H5N1 variants. They showed for the first time that the 2022 mutant is better at binding to these cells and replicating within them. . “Bad news,” van Riel says.

“I don’t think it’s extremely likely that the virus will become a pandemic,” she says. However, the fact that this virus is better at infecting humans gives it more opportunity to acquire further mutations, increasing the likelihood of a pandemic.

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

Currently, H5N1 hemagglutinin primarily binds to receptors located deep in the lungs in humans. This means that although it can cause serious illness, it is unlikely to leave the body and infect others. For that to happen, the virus needs to infect the cells inside your nose and throat. This means that coughing and sneezing can expel the virus and infect others.

Van Riel's research suggests that the virus can do this to some extent, but it is not clear whether the virus binds to the main receptors on these cells. It was thought that multiple mutations were required for H5N1 to bind strongly to these receptors, but Wilson's team now shows that a single mutation is sufficient for the current H5N1 variants. Showed.

Team members say this change alone won’t prevent the virus from causing a pandemic. Jim Paulsonalso at the Scripps Research Institute. “We think this property is necessary, but importantly not sufficient, for pandemic virus transmission,” he says.

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

However, if H5N1 viruses that infect humans acquire receptor switching mutations, they may evolve these other changes as well.

Furthermore, it is possible, in theory, to acquire all the necessary abilities at once by exchanging genes with a human virus that infects the same individual. Several previous influenza pandemics have been caused by genetic swapping between animal and human influenza viruses, Paulson said.

“This is very worrying,” he says alice katsurakis from the University of Oxford was not involved in either study. “Every time it spreads to humans, it gives the virus a roll of the dice.”

What is the mortality rate of the H5N1 pandemic?

If H5N1 avian influenza begins to spread from person to person, the big question is how deadly it will be. Half of the people confirmed to have contracted the virus since 2003 have died. However, the actual infection fatality rate is likely to be even lower, as many cases likely go undetected and mild cases are likely to be missed.

Of the roughly 60 people infected in the U.S. since the dairy outbreak began, nearly all have had only mild symptoms. why not understoodbut one explanation is that many were infected through the eyes. “It’s known to have much more benign results,” Katzorakis says.

It is also thought to become less dangerous when the virus switches from binding to receptors deep in the lungs to binding to receptors in the upper airways. But puzzling aspects of the U.S. cases left Paulson unsure whether this also applied to H5N1. “To be honest, I don’t know what to think right now,” he says.

“I don’t think there’s any reason to be satisfied with this and expect that even if this virus were to be easily transmitted from person to person, it would be ‘mild,'” Katzourakis said.

Because Wilson’s team studied the hemagglutinin protein alone, there was no chance that the mutated protein could leak into the lab. “No viruses were used here at all,” he says.