by In early March, Dr. Barb Petersen, a large animal veterinarian in Texas, gets calls from the dairy farms she works with in the Panhandle. Workers there saw mastitis on many cows, an infection of the udder.
Their milk was thickened and discolored, and none of the usual suspects like bacteria or tissue damage could explain it.
Dairy some other called. One owner told her he thought his farm had “whatever was going on, and half my pets have died,” indicating the contamination had spread beyond cattle.
After running a battery of tests and ruling out every cause she could think of, Petersen sent samples from sick and dead animals to the Texas A&M state veterinary laboratory and to friends and colleagues at Iowa State University.
What they found – loads of the H5N1 flu virus – shocked the dairy industry and alerted public health officials around the world. He also created an urgent scientific to-do list. One of the first questions to be answered was how the virus was infecting cows in the first place.
Researchers in the US and Denmark took up that task. Their results, published as a preprint study, show that cows have the same receptors for flu viruses as humans and birds. Scientists fear that cows may be mixing bowls – a host that helps the virus learn how to spread better between people. Such an event, though rare, experts say, could put us on the path to another pandemic.
Bird flu tries new hosts
For years, H5N1, or the highly pathogenic avian flu, has been mainly confined to the bird population, but recently it has begun to infect an increasing number of mammals, suggesting that the virus may be adapting and moving closer to being a human pathogen.
Avian flu viruses have decimated commercial poultry flocks in the US, and because pigs are known to catch bird flu viruses, pigs were closely monitored for signs of infection – but cows were not on anyone’s radar as potential hosts .
Since the end of March, 42 infected herds have been found in nine states, according to the US Department of Agriculture. Only one person has been found to be infected with H5N1 after contact with infected cows, and the US Centers for Disease Control and Prevention says the current risk to public health is low, although it is working with states to monitor people with animal exposures.
“The decision in cattle was so different,” said Dr. Lars Larsen, professor of clinical veterinary microbiology at the University of Copenhagen in Denmark. In mammals, influenza usually infects the lungs. In cats, it can also infect the brain. “Here we see a huge amount of virus in the mammary and the milk,” Larsen said.
Larsen said the concentration of H5N1 viruses in infected cow’s milk is 1,000 times higher than typically seen in infected birds. He said he and his colleagues calculated that even if the milk from one infected cow was diluted in 1,000 tonnes of milk, scientists would still be able to pick up traces of the virus in laboratory tests.
Tests by the US Food and Drug Administration found inert fragments of genetic material from the H5N1 virus in about 1 in 5 samples of milk bought on grocery store shelves, raising questions about how the virus became so widespread . Researchers confirmed in later tests that the pasteurized milk he tested was not contagious and could not make anyone sick.
That didn’t stop the outburst from fraying more than a few nerves. Big money is riding on cow health. Milk and dairy products were the fourth largest agricultural commodity in the US in terms of cash receipts in 2022, according to the USDA’s economic research service. The sale of cattle and calves was the second largest commodity.
How viruses break into cells
Viruses need a way to hack into cells. For the virus that causes Covid-19, the key is a receptor called ACE2. For flu viruses, it’s a sugar molecule that sticks out from the surface of cells called sialic acid.
Different animals carry different forms, or shapes, of sialic acids. Birds have slightly different shapes of sialic acid receptors than humans in their upper respiratory tract.
If you hold your index finger straight up, that’s what a bird’s sialic acid receptor looks like, says Dr. Andy Pekosz, a molecular microbiologist and immunologist at Johns Hopkins University. If you bend your finger at the knuckle into an upside down L, that’s what a human silicic acid receptor looks like. Influenza viruses generally prefer to bind to one shape over another, he said.
Researchers think this may be one reason why H5N1, which originated from birds, has not been shown to spread efficiently between humans.
Until recently, no one knew what type of sialic acid receptors they were, as it was believed that they did not catch A-strain influenza viruses such as H5N1.
Larsen and his colleagues in the US and Denmark took tissue samples from the lungs, windpipes, brains and mammary glands of calves and cows and stained them with compounds they knew would bind to different types of sialic acid receptors. They sliced the stained tissues very thinly and viewed them under a microscope.
What they saw was surprising: The little milk sacs of the udder, called alveoli, were full of sialic acid receptors, and they had both the types of receptors associated with birds and those more common in humans. Almost every cell they looked at had both types of receptors, said lead study author Dr. Charlotte Kristensen, a postdoctoral researcher in veterinary pathology at the University of Copenhagen.
That finding raised concerns because one way flu viruses change and evolve is by exchanging pieces of their genetic material with other flu viruses. This process, called reassortment, requires a cell to be infected with two different influenza viruses at the same time.
“If you get both viruses in the same cell at the same time, you can essentially end up with hybrid viruses,” said study author Dr. Richard Webby, director of the World Health Organization’s Collaborating Center for the Study of Ecology Influenza in Animals and Birds.
To be simultaneously infected with two flu viruses – a bird flu virus and a human flu virus – would require the presence of two types of sialic acid receptors in a cell, which cows do, which was not known before this study.
“I think this is probably a fairly rare event,” said Webby, who has been studying the H5N1 virus for 25 years.
For such a thing to happen, a cow infected with the bird flu virus would have to pick up another strain of the flu from an infected person. Currently, human flu infections are low across the country and falling as the flu season progresses, making the chance of something like this even more remote.
Still, it’s not unheard-of.
Pigs also have human and avian silicic acid receptors in their respiratory tract, and influenza infections in pigs are known to trigger pandemic viruses. The 2009 pandemic caused by H1N1 flu, for example, is believed to have started in pigs in Mexico when the virus reassorted to be able to spread rapidly between humans.
Another way the bird flu virus could change in cows, Webby says, is more gradually — and more commonly.
Every time a virus copies itself, it makes mistakes. Sometimes, those mistakes make the virus stronger and hurt their chances of survival, but in other cases, they are happy accidents – at least for the virus. If a bird flu virus mutated in a way that made it able to bind more easily to the human-type sialic acid receptors in cows, it could gain a survival advantage: the ability to infect more cells infection and more types of animals, for example. people.
Viruses can transfer and flow
Reassortment would be a major change in the evolution of the virus, but the gradual transfer of the virus through new hosts could lead to a change in the genome of the virus through evolutionary drift.
Either way, it’s not good news, said Dr. Sam Scarpino, a computational biologist and director of AI and life sciences at Northeastern University.
“We now have a piece of data that suggests the risk profile is higher,” said Scarpino, who was not involved in the new study.
He notes that this is early research. It needed to be confirmed by another group of researchers, and was quickly published as a preprint before being scrutinized by outside experts.
But he said the findings are also important because no one had really looked at the susceptibility of cow tissue to influenza A viruses before.
“This is the first I know of. It doesn’t mean there isn’t another one out there, but some of us looked carefully and we didn’t find one,” he said.
Kristensen also said the researchers couldn’t find any prior research on it, which is why they did the study.
“We felt that, given the situation, we should get these results out as quickly as possible,” Larsen said.
Other experts said that while there are more dots to connect, the study clearly raises the alarm level.
“I think we have more than enough information now to conclude that what is going to happen is that we need to stop transmission in dairy cattle,” Scarpino said. “We need to increase the types of protection that are mandated for workers in close contact with cows and milk products and significantly increase the funding that is going to understanding influenza and cows, because there is only so much huge that we don’t know. which we must learn very quickly.”
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