Cows have human flu receptors, study shows, raising risks of bird flu outbreak in dairy cattle

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In early March, Dr. Barb Petersen, a large animal veterinarian in Texas, began receiving calls from the dairy farms she works with in the Panhandle. Workers saw many cows with mastitis, an infection of the udder.

Her milk was thick and discolored, and none of the usual suspects, like bacteria or tissue damage, could explain it.

Several more dairies called. One owner told him that he thought his farm had “whatever’s going on, and half my pets have died,” indicating that the contagion had gone beyond the livestock.

After running a series of tests and ruling out every cause he could think of, Petersen sent samples of 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 influenza virus — has shaken the dairy industry and put public health officials around the world on alert. He also created an urgent scientific task list. One of the first questions that needed to be answered was how the virus infected cows in the first place.

Researchers from the United States 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 cows could be mixing bowls, hosts that help the virus learn to spread better between people. Such an event, although rare, experts say, could put us on the path to another pandemic.

For years, H5N1, or highly pathogenic avian influenza, has been mainly limited to the bird population, but it has recently begun infecting an increasing number of mammals, suggesting that the virus could be adapting and moving closer to becoming a human pathogen.

Avian flu viruses have decimated commercial poultry in the US, and since pigs are known to contract avian flu viruses, pigs have been closely monitored for signs of infection, but the Cows weren’t on anyone’s radar as potential guests.

Since late March, 42 infected herds have been found in nine states, according to the U.S. Department of Agriculture. Only one person has been infected with H5N1 after contact with infected cows, and the U.S. Centers for Disease Control and Prevention says the current risk to public health is low, although they are working with states to monitor people exposed to animals.

“The finding in cattle has been very different,” said Dr. Lars Larsen, a professor of veterinary clinical microbiology at the University of Copenhagen in Denmark. In mammals, the flu 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 virus in the milk of infected cows is 1,000 times higher than that normally seen in infected birds. He said he and his colleagues calculated that even if milk from a single infected cow were diluted in 1,000 tons of milk, scientists would still be able to detect traces of the virus in laboratory tests.

Testing by the U.S. Food and Drug Administration found inert fragments of genetic material from the H5N1 virus in about 1 in 5 milk samples purchased from grocery store shelves, raising questions about how the virus spread. had spread so much. The researchers confirmed in subsequent tests that the pasteurized milk they tested was not infectious and could not make anyone sick.

That hasn’t stopped the outbreak from making more than a few nervous. There is a lot of money at stake in cow health. Milk and dairy products were the fourth-largest agricultural product in the U.S. in terms of cash receipts in 2022, according to the USDA Economic Research Service. Sales of cattle and calves were the second most important product.

Viruses need a way to hack into cells. For the virus that causes Covid-19, the key is a receptor called ACE2. In the case of flu viruses, it’s a sugar molecule that protrudes from the surface of cells called sialic acid.

Different animals carry different forms or forms of sialic acids. Birds have sialic acid receptors that have slightly different shapes than humans have in their upper respiratory tracts.

If you hold your index finger up, this is 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 inverted L, this is what the human sialic acid receptor looks like. Flu viruses tend to prefer binding to one form over the other, he said.

Researchers believe this may be one reason why H5N1, which originated in birds, has not been shown to spread efficiently among people.

Until recently, no one knew what type of sialic acid receptors cows had, because it was believed that they did not contract strain A flu viruses like H5N1.

Larsen and his colleagues in the United States and Denmark took tissue samples from the lungs, tracheas, 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 cut the dyed tissues into very thin slices and observed them under a microscope.

What they saw was surprising: The tiny milk-producing udder sacs, called alveoli, were packed with sialic acid receptors, and they had both the type of receptors associated with birds and those more common in people. Almost all of the cells they looked at contained both types of receptors, said the study’s lead author, Dr. Charlotte Kristensen, a postdoctoral researcher in veterinary pathology at the University of Copenhagen.

That finding has raised concerns because one way flu viruses change and evolve is by exchanging parts of their genetic material with other flu viruses. This process, called recombination, requires a cell to be infected with two different flu viruses at the same time.

“If you have both viruses in the same cell at the same time, you can essentially get hybrid viruses,” said study author Dr. Richard Webby, director of the Collaborating Center for Studies on Influenza Ecology at the World Health Organization. health. in Animals and Birds.

To be infected simultaneously with two flu viruses (an avian flu virus and a human flu virus), a cell would need to have both types of sialic acid receptors, 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 contract a different strain of flu than an infected human. Currently, human flu infections are low nationwide and declining as the flu season comes to an end, making the chance of something like this happening even more remote.

Still, it’s not unheard of.

Pigs also have both human and avian sialic acid receptors in their respiratory tracts, and influenza infections in pigs are known to cause pandemic viruses. The 2009 pandemic caused by H1N1 influenza, for example, is believed to have started in pigs in Mexico when the virus reassorted to become one that could spread rapidly among people.

Another way the bird flu virus might 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 potent and hurt its chances of survival, but in other cases they are happy accidents, at least for the virus. If the bird flu virus changed so that it could bind more easily to human-type 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 change and drift

Recombination would be a big change 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 genome 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 data that suggests the risk profile is higher,” said Scarpino, who was not involved in the new study.

He points out that this is a preliminary investigation. It needs to be confirmed by a different group of researchers, and was quickly published as a preprint before scrutiny by outside experts.

But he said the findings are also important because no one had previously analyzed the susceptibility of cow tissues to influenza A viruses.

“This is the first time I am aware of it. “It doesn’t mean there isn’t another one out there, but several of us looked at it pretty closely and didn’t find any,” he said.

Kristensen said the researchers also couldn’t find any previous research on this, which is why they did the study.

“We just felt that, given the situation, we should get these results as quickly as possible,” Larsen said.

Other experts said that although there are more dots to connect, the study clearly raises the level of alert.

“I think we now have more than enough information to conclude that what needs to happen is to stop transmission in dairy cattle,” Scarpino said. “We need to increase the types of protection required for workers who are in close contact with cows and dairy products and significantly increase the funds dedicated to understanding influenza and in cows, because there is a huge amount that we don’t know. that we need to learn very quickly ”.