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In early March, Texas large animal veterinarian Dr. Barb Petersen started receiving calls from dairy farms she works with in the Panhandle. Workers there were treating many cows with mastitis, an infection of the udder.
Their milk was thick and discolored and could not be explained by the usual suspects such as bacteria or tissue damage.
Several more dairy farms called. One pet owner told her she thought “what’s going on is half her pets are dead” on her farm, suggesting her infection has spread beyond the cows. did.
After conducting a series of tests and ruling out all possible causes, Petersen sent samples of sick and dead animals to friends and colleagues at the Texas A&M State Veterinary Laboratory and Iowa State University.
The large numbers of H5N1 influenza viruses they discovered shook the dairy industry and alarmed public health authorities around the world. An urgent science to-do list was also created. One of the first questions that had to be answered was how the virus infected cows in the first place.
Researchers from the United States and Denmark took on the task. Their discovery is preprint Studies have shown that cows have the same receptors for influenza viruses as humans and birds. Scientists are concerned that cows may be mixing the bowls. This is the host that helps the virus learn to spread better between people. Although such events are rare, experts say they could put us on the path to another pandemic.
For many years, H5N1 (highly pathogenic avian influenza) was primarily restricted to birds, but recently it has begun to infect more and more mammals, raising the possibility that this virus may be adapting and becoming more of a human pathogen. It is suggested that there is a sex.
Avian influenza virus has devastated commercial poultry flocks in the United States. Pigs have been closely monitored for signs of infection, as they are known to be infected with avian influenza viruses, but cattle have remained largely unnoticed as potential hosts.
According to the U.S. Department of Agriculture, 42 infected herds have been found in nine states since late March. He is the only person known to have been infected with H5N1 after contact with infected cattle, and the U.S. Centers for Disease Control and Prevention says the current risk to public health is low, but low at this time. . Work with states to monitor people exposed to animals.
“The findings in cows are 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, the brain can also be infected. “What we see here is a huge amount of virus present in the breast and milk,” Larsen said.
Larsen said the concentration of H5N1 virus in the milk of infected cows was 1,000 times higher than the concentration typically seen in infected birds. He and his colleagues said they calculated that even if they diluted the milk from one infected cow with 1,000 tons of milk, scientists would still be able to detect traces of the virus in clinical tests. .
Tests by the U.S. Food and Drug Administration have found inactive fragments of the H5N1 virus’ genetic material in about one in five milk samples purchased on grocery store shelves, explaining how the virus became so widespread. The question arose: In subsequent tests, researchers confirmed that the pasteurized milk they tested was not infectious and could not make people sick.
However, this did not stop many people from feeling anxious due to the spread of infection. A huge amount of money is invested in the health of cows. Milk and dairy products were her fourth largest agricultural product in the United States in terms of cash income in 2022. according to USDA Economic Research Service. Cow and calf sales were his second largest product.
Viruses need a way to hack cells. The key to the virus that causes Covid-19 is a receptor called ACE2. In the case of the influenza virus, it’s a sugar molecule that protrudes from the surface of cells called sialic acid.
Different animals possess different forms of sialic acid. Birds have sialic acid receptors that are shaped slightly differently than those found in humans’ upper respiratory tract.
Dr. Andy Pekosch, a molecular microbiologist and immunologist at Johns Hopkins University, says that when you hold your index finger straight up, it becomes similar to a bird’s sialic acid receptor. That’s what human sialic acid receptors look like when you bend your fingers into an inverted L shape. Influenza viruses tend to prefer binding to some shapes over others, he said.
Researchers believe this may be one reason why the H5N1 virus, which originates from birds, has not been shown to transmit efficiently between humans.
Until recently, no one knew what kind of sialic acid receptors cows had because it was thought that cows were not susceptible to influenza A viruses such as 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 known to bind to different types of sialic acid receptors. They sliced the stained tissue into very thin slices and viewed them under a microscope.
What they saw was amazing. The tiny milk-producing sacs in the breasts, called alveoli, were full of sialic acid receptors, both the kind associated with birds and those more common in humans. Dr. Charlotte Christensen, a postdoctoral fellow in veterinary pathology at the University of Copenhagen and lead author of the study, said that nearly all the cells they observed contained both types of receptors.
The discovery raises concerns because one of the ways influenza viruses change and evolve is by exchanging some of their genetic material with other influenza viruses. This process, called reassortment, requires cells to be infected with two different influenza viruses at the same time.
“If you infect the same cell with both viruses at the same time, you could essentially have a hybrid virus come out of it,” said study author Dr. Richard Webby, director of the World Health Organization Collaborating Center for Influenza Ecology. Ta. with animals and birds.
To be simultaneously infected with two influenza viruses, an avian influenza virus and a human influenza virus, cells must have both types of sialic acid receptors, which cows have; This was unknown prior to the study.
“I think this is probably a pretty rare event,” said Webby, who has studied H5N1 viruses for 25 years.
For that to happen, cows infected with the avian influenza virus would need to transmit a different strain of influenza from an infected human. This is even less likely because the number of human influenza infections is currently low nationwide and declining as the flu season ends.
Still, it’s not unprecedented.
Additionally, pigs have both human and avian sialic acid receptors in their respiratory tract, and influenza infection in pigs is known to cause pandemic viruses. For example, the 2009 pandemic caused by H1N1 influenza is believed to have started this pandemic. mexican pig When the virus reassembles into a virus that can spread rapidly between people.
Another way avian influenza viruses change in cattle is more gradual and more common, Webby said.
Viruses make mistakes every time they copy themselves. Sometimes these mistakes weaken the virus’s potency and hurt its chances of survival, but sometimes it’s a happy coincidence, at least for the virus. If the avian influenza virus happens to change in a way that makes it easier to 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. there is. human.
Viruses can move or drift
Reassortment represents a major change in virus evolution, but evolutionary drift can also change the viral genome as the virus gradually passes through new hosts.
Either way, this is not good news, said Dr. Sam Scarpino, a computational biologist and director of AI and life sciences at Northeastern University.
“We have data that suggests a higher risk profile,” said Scarpino, who was not involved in the new study.
He points out that this is early research. It required confirmation by another group of researchers and was quickly published as a preprint before being reviewed by external experts.
But he said the discovery was also important because, until now, no one had seriously considered the susceptibility of cow tissue to influenza A viruses.
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“This is the first I’ve heard of it. It doesn’t mean there aren’t others, but some of us looked at it carefully and found nothing,” he said.
Christensen said the researchers conducted the study because they also couldn’t find any previous studies on it.
“Given the circumstances, we felt it necessary to announce these results as soon as possible,” Larsen said.
Other experts said that while there are still connections to be made, the study clearly raises the level of alarm.
“I think we now have enough information to conclude that we need to stop infection in dairy cows,” Scarpino said. “We need to increase the types of protections required for workers who come into close contact with cows and dairy products, and significantly increase funding for understanding influenza and cows, because there is so much we don’t know. ” We need to learn very quickly. ”
