At the beginning of 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 many cows with mastitis, an udder infection.
Their milk was thickened and discolored, and this couldn't be explained by the usual suspects like bacteria or tissue damage.
A number of other dairies called. One owner told her he thought his farm "had everything going on, and half of my pets had died," indicating the infestation had spread beyond just livestock.
After running a series 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 - a lot of the H5N1 flu virus - has rocked the dairy industry and put public health officials around the world on alert. It also created an urgent scientific to-do list. One of the first questions to be answered was how the virus infected cows in the first place.
Researchers in the US and Denmark took on that task. Their findings, published as a preprint study, show that cows have the same receptors for flu viruses as humans and birds. Scientists fear that cows could be mixing bowls - hosts that help the virus spread better among people. Such an event, while rare, experts say, could put us on the path of another pandemic.
Bird flu is trying out new hosts
For years, H5N1, the highly pathogenic bird flu, was mainly confined to bird populations, but recently it has begun to infect a growing number of mammals, indicating that the virus may be adapting and moving closer to becoming a human pathogen.
Bird flu viruses have decimated commercial poultry flocks in the US, and because pigs are known to contract bird flu viruses, pigs are closely watched for signs of infection - but cows were not on anyone's radar as potential hosts.
According to the U.S. Department of Agriculture, 42 infected herds have been found in nine states since the end of March. Only one person has been found to be infected with H5N1 after contact with infected cows, and the U.S. Centers for Disease Control and Prevention says the current public health risk is low, although they are working with states to monitor people with animal exposure.
"The findings in cattle were so different," says Dr. Lars Larsen, professor of veterinary clinical 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 breast and in the milk," Larsen said.
Larsen said the concentration of H5N1 viruses in the milk of infected cows is a thousand times higher than normally seen in infected birds. He said he and his colleagues had calculated that even if the milk from a single infected cow were diluted in 1,000 tons of milk, scientists would still be able to pick up traces of the virus in laboratory tests.
U.S. Food and Drug Administration testing has found inert fragments of genetic material from the H5N1 virus in about 1 in 5 samples of milk purchased on supermarket shelves, raising questions about how the virus became so widespread. Researchers confirmed in later tests that the pasteurized milk they tested was not contagious and could not make anyone sick.
That hasn't stopped the outbreak from rattling more than a few nerves. A lot of money is invested in cow health. Milk and dairy products were the fourth-largest agricultural commodity in the U.S. in terms of cash revenues in 2022, according to the USDA Economic Research Service. Sales of cattle and calves were the second largest commodity.
How viruses enter 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 is a sugar molecule that protrudes from the cell surface, called sialic acid.
Different animals carry different forms or forms of sialic acids. Birds have sialic acid receptors that differ slightly from the shape humans have in their upper airways.
If you hold your index finger straight up, a bird's sialic acid receptor looks something like this, 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, this is what the human sialic acid receptor looks like. Flu viruses tend to bind to one form over another, he said.
Researchers believe this may be one reason why H5N1, which originated in birds, has not been shown to spread efficiently between humans.
Until recently, no one knew what type of sialic acid receptors cows had, because it was thought they did not contract influenza A viruses such as H5N1.
Larsen and his colleagues in the US and Denmark took tissue samples from the lungs, trachea, brains and mammary glands of calves and cows and stained them with compounds they knew would attach to different types of sialic acid receptors. They cut the stained tissues very thinly and looked at them under a microscope.
What they saw was surprising: The udder's tiny milk-producing sacs called alveoli were packed with sialic acid receptors, and they had both the kind of receptors associated with birds and the kind of receptors more common in humans. Nearly every cell they looked at contained both types of receptors, said lead study author Dr. Charlotte Kristensen, a postdoctoral researcher in veterinary pathology at the University of Copenhagen.
This finding has 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 that a cell be infected with two different flu viruses at the same time.
"If you get both viruses into the same cell at the same time, you can essentially get hybrid viruses out of it," says study author Dr. Richard Webby, director of the World Health Organization's Collaborating Center for Studies on the Ecology of Influenza. in Animals and Birds.
To be infected simultaneously with two flu viruses - a bird flu virus and a human flu virus - a cell would have to have both types of sialic acid receptors, which cows do, something that was not known before this study.
"I think this is probably a pretty rare event," said Webby, who has been studying the H5N1 virus for 25 years.
For something like this to happen, a cow infected with the bird flu virus would have to pick up a different strain of flu than an infected human. Currently, human flu infections are low nationwide and declining as flu season winds down, making the possibility of something like this happening even less likely.
Yet it is not unheard of.
Pigs also have both human and avian sialic acid receptors in their respiratory tract, and influenza infections in pigs are known to cause pandemic viruses. For example, the 2009 pandemic caused by the H1N1 flu is believed to have started in pigs in Mexico, when the virus evolved into one that could spread quickly between people.
Another way the bird flu virus can change in cows, Webby says, is more gradual - and more common.
Every time a virus copies itself, it makes mistakes. Sometimes those mistakes make the virus less powerful and reduce its chances of survival, but in other cases they are happy accidents - at least for the virus. If an avian flu virus were to change so that it could more easily bind to human sialic acid receptors in cows, it could gain a survival advantage: the ability to infect more cells and more types of animals, such as humans.
Viruses can move and drift
Reassortment would represent a major shift in the evolution of the virus, but the gradual passage of the virus through new hosts could also result in a change in the virus's genome through evolutionary drift.
Either way, it's not good news, says Dr. Sam Scarpino, a computational biologist and director of AI and life sciences at Northeastern University.
"We now have 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 needs to be confirmed by another group of researchers, and it was quickly published as a preprint before being examined by outside experts.
But he said the findings are also important because no one had really looked at the susceptibility of cow tissues to influenza A viruses before.
"This is the first thing I'm aware of. "It doesn't mean there isn't another one, but a number of us have looked quite closely and haven't found one," he said.
Kristensen said researchers couldn't find any previous research on it either, which is why they did the investigation.
"We just felt that given the situation, we had to go out with these results as quickly as possible," Larsen said.
Other experts said that while there are more dots to connect, the research clearly raises alert levels.
"I think we now have more than enough information to conclude that what needs to happen is we need to stop transmission among dairy cattle," Scarpino said. "We need to increase the types of protection that are mandatory for workers who are in close contact with cows and dairy products, and significantly increase the funding spent on understanding influenza and in cows, because there is just a huge amount that we not knowing. that we have to learn very quickly."
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