Cows have human flu receptors, study shows, raising the stakes on the bird flu outbreak in dairy cattle

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

Their milk was thickened and discolored, and it couldn’t be explained by any of the usual suspects like bacteria or tissue damage.

Several other dairies called. One owner told him he thought his farm had “everything going on, and half my pets died,” indicating that the contagion had spread beyond livestock.

After running a battery of tests and ruling out every cause she 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 the University. of Iowa State.

What they discovered – a large quantity of the H5N1 flu virus – shook the dairy industry and put public health officials around the world on alert. He also created a list of urgent scientific tasks. One of the first questions to be answered was how the virus infected cows in the first place.

American and Danish researchers took on this task. Their results, published as a preliminary study, show that cows have the same receptors for influenza viruses as humans and birds. Scientists worry that cows are mixing bowls – hosts that help the virus spread better between humans. Such an event, while rare, experts say, could put us on the path to another pandemic.

For years, the H5N1 virus, or highly pathogenic avian influenza, was primarily limited to the bird population, but it has recently begun to infect increasing numbers of mammals, suggesting that the virus may adapt and approaching its status as a pathogen for humans.

Bird flu viruses have decimated commercial poultry farms in the United States, and because pigs are known to catch bird flu viruses, pigs have been closely monitored for any signs of infection – but cows weren’t on anyone’s radar as potential hosts.

Since the end of March, 42 infected herds have been discovered 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 public health risk is low, although it is working with states to monitor people exposed to animals.

“The results in cattle were very different,” said 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 virus in the milk of infected cows is 1,000 times higher than that typically seen in infected birds. He said he and his colleagues had calculated that even if milk from a single infected cow was diluted into 1,000 tonnes of milk, scientists would still be able to detect traces of the virus in laboratory tests.

Tests by the U.S. Food and Drug Administration have found inert fragments of genetic material from the H5N1 virus in about 1 in 5 milk samples purchased on grocery store shelves, raising questions about how the virus spreads. is widespread. Researchers confirmed in subsequent tests that the pasteurized milk tested was not infectious and could not make anyone sick.

That didn’t stop the outbreak from rattling more than a few nerves. Large investments depend on the health of cows. Milk and dairy products were the fourth largest agricultural commodity in the United States in terms of cash receipts in 2022, according to the USDA Economic Research Service. Cattle and calf sales were the second largest product.

Viruses need a way to hijack cells. For the virus responsible for Covid-19, the key is a receptor called ACE2. For flu viruses, this is a sugar molecule that protrudes from the cell surface, called sialic acid.

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

If you hold your right index finger 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 to form an upside-down L, this is what the human sialic acid receptor looks like. Flu viruses tend to prefer to bind to one form over another, he said.

Researchers believe this could be one reason why H5N1, which originated in birds, does not spread effectively between humans.

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

Larsen and colleagues in the United States and Denmark took tissue samples from the lungs, trachea, brain, and mammary glands of calves and cows and stained them with compounds they knew bind to different types of sialic acid receptors. They cut the stained tissue very finely and examined it under a microscope.

What they saw was surprising: The tiny milk-producing sacs in the udder, called alveoli, were teeming with sialic acid receptors, and they had both the type of receptors associated with birds and those more common in humans. Almost all cells examined 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.

This finding raised concerns because one of the ways 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 simultaneously.

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

To be infected with two influenza viruses simultaneously – an avian flu virus and a human flu virus – a cell would need to have both types of sialic acid receptors, which cows have, which does not was not known before this study.

“I think this is probably a pretty rare event,” said Webby, who has studied the H5N1 virus for 25 years.

For such a thing to happen, a cow infected with the avian 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 draws to a close, making the possibility of such a situation occurring even more remote.

However, it is not unknown.

Pigs also have human and avian sialic 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 retooled into one capable of spreading quickly between people.

Another way the bird flu virus could evolve in cows, Webby says, is more gradual — and more common.

Every time a virus copies itself, it makes mistakes. Sometimes these mistakes make the virus less powerful and hurt 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 binds more easily to human-type sialic acid receptors in cows, it could gain a survival advantage: the ability to infect more cells and more animals. types of animals, like humans.

Viruses can move and drift

Reassortment would constitute a significant change in the evolution of the virus, but the gradual passage of the virus through new hosts could also result in modification of 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 notes that this is initial research. This needs to be confirmed by another group of researchers, and it was quickly released as an upcoming preprint…