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

A recent study has revealed that cows have receptors for human flu viruses, raising concerns about the potential outbreak of bird flu in dairy cattle. Veterinarian Dr. Barb Petersen first noticed an increase in cases of mastitis, a udder infection, on the dairy farms she works with in Texas. The milk from these cows appeared thickened and discolored, with no obvious explanation. As more dairy farms reported similar symptoms, it became clear that the contagion had spread beyond cattle. Tests conducted by Texas A&M state veterinary lab and Iowa State University identified the presence of the H5N1 influenza virus, causing alarm within the dairy industry and alerting public health officials worldwide. To understand how the virus was infecting cows, researchers in the US and Denmark investigated further. Their findings, published as a preprint study, indicate that cows possess the same flu virus receptors as humans and birds, raising concerns that cows could serve as hosts for the virus to evolve and better transmit to humans. While such events are rare, experts warn that it could potentially lead to another pandemic.
In recent years, there has been a concerning development with H5N1, also known as highly pathogenic avian influenza. While it has mainly affected birds, there is growing evidence that the virus is starting to infect mammals, raising the possibility of it becoming a human pathogen.

The avian flu has wreaked havoc on commercial poultry in the US, and pigs have been closely monitored as they can catch bird flu viruses. However, cows were not considered potential hosts until recently.

According to the US Department of Agriculture, 42 infected herds have been discovered in nine states since late March. So far, only one person has been found to be infected with H5N1 after coming into contact with infected cows. The US Centers for Disease Control and Prevention states that the current risk to public health is low, but they are working with states to monitor individuals who have had animal exposures.

Dr. Lars Larsen, a professor of veterinary clinical microbiology at the University of Copenhagen, explained that the findings in cattle have been quite different. In mammals, influenza typically affects the lungs, but in cats, it can also infect the brain. In the case of infected cows, an unusually high amount of the virus has been found in the mammary glands and milk.

Larsen revealed that the concentration of H5N1 viruses in the milk of infected cows is 1,000 times higher than what is typically seen in infected birds. Even if the milk from a single infected cow were diluted in 1,000 tons of milk, traces of the virus would still be detectable in lab tests, according to calculations made by Larsen and his colleagues.
Recent tests conducted by the US Food and Drug Administration revealed that approximately 20% of milk samples purchased from grocery stores contained fragments of genetic material from the H5N1 virus. This discovery has raised concerns regarding the widespread presence of the virus. However, subsequent tests confirmed that the pasteurized milk was not infectious and posed no risk to human health.

Despite the lack of danger, the outbreak has caused anxiety among many individuals. The economic implications are significant, as the health of cows plays a crucial role in the dairy industry. In fact, milk and dairy products ranked fourth in terms of cash receipts among agricultural commodities in the US in 2022, according to the USDA’s economic research service. Additionally, sales of cattle and calves were the second largest commodity.

Understanding how viruses infiltrate cells is essential in comprehending their spread. The Covid-19 virus, for example, targets a receptor called ACE2, whereas flu viruses are attracted to a sugar molecule called sialic acid protruding from cell surfaces.

Different forms of sialic acids exist in various animals. Birds, for instance, possess slightly different-shaped sialic acid receptors compared to those found in the upper respiratory tracts of humans.

Dr. Andy Pekosz, a molecular microbiologist and immunologist at Johns Hopkins University, explains that a bird’s sialic acid receptor resembles an upward-pointing index finger, while a human’s receptor appears like a bent finger forming an upside-down L shape. Flu viruses tend to favor binding to one shape over the other.

Researchers believe that this disparity may be one reason why H5N1, originating from birds, has not efficiently transmitted between humans.
Until recently, it was believed that cows were not susceptible to A-strain flu viruses like H5N1, and little was known about their sialic acid receptors. However, a recent study conducted by Larsen and his colleagues in the US and Denmark shed new light on this subject. They collected tissue samples from calves and cows and used specific compounds to stain the samples, allowing them to identify different types of sialic acid receptors. Through microscopic analysis, they discovered that the milk-producing sacs in the udder, known as alveoli, were abundant with sialic acid receptors. Surprisingly, these receptors included both types associated with birds and those more commonly found in humans. Lead study author Dr. Charlotte Kristensen explained that almost every cell they examined contained both types of receptors. This finding is concerning because flu viruses can undergo reassortment, a process in which they exchange genetic material with other flu viruses. Reassortment requires a cell to be infected with two different flu viruses simultaneously. Dr. Richard Webby, a study author and director of the World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds, explained that if a cell possesses both types of sialic acid receptors, it can produce hybrid viruses through reassortment. This study revealed that cows have the potential to be simultaneously infected with bird flu viruses and human flu viruses, a previously unknown phenomenon.
“I believe that this occurrence is likely to be quite rare,” commented Webby, a seasoned researcher of the H5N1 virus for over two decades.

For an event like this to transpire, it would require a cow infected with the avian flu virus to contract a different strain of flu from an infected human. Currently, human flu infections are minimal and decreasing as the flu season comes to an end, which makes the likelihood of such an event even more remote.

Nevertheless, it is not unheard of.

Pigs also possess both human and bird sialic acid receptors in their respiratory tracts, and flu infections in pigs have been known to give rise to pandemic viruses. For instance, the 2009 H1N1 influenza pandemic is believed to have originated in Mexican pigs when the virus underwent reassortment, enabling it to spread rapidly among humans.

Webby also suggests that the bird flu virus could undergo more gradual, yet more common, changes in cows.

Whenever a virus replicates itself, errors are made. Sometimes, these mistakes weaken the virus and hinder its chances of survival, but in other cases, they lead to fortunate accidents – at least for the virus. If a bird flu virus were to change in a way that facilitated easier binding to human-type sialic acid receptors in cows, it would gain a survival advantage: the ability to infect more cells and various types of animals, including humans.

Viruses have the ability to shift and drift.

Reassortment would signify a significant shift in the virus’ evolution, but the gradual passage of the virus through new hosts could also result in changes to its genome through evolutionary drift.

Either way, this is not positive news, warned Dr. Sam Scarpino, a computational biologist and director of AI and life sciences at Northeastern University.
“This new study suggests a higher risk profile,” explained Scarpino, a researcher not involved in the study. However, he emphasizes that this is early research and needs to be verified by other experts. The study was published quickly as a preprint, allowing for outside scrutiny.

Scarpino also highlights the significance of the findings, as no previous research has delved into the susceptibility of cow tissues to influenza A viruses. He acknowledges that while there may be other studies out there, none were found by the researchers involved in this study.

The urgency to publish the results quickly stems from the lack of prior research on the topic. Larsen, one of the researchers, explains that given the current situation, it was crucial to share the findings as soon as possible.

Experts agree that while there are still connections to be made, the study raises concerns and warrants a higher level of alert. Scarpino stresses the need to halt transmission in dairy cattle and implement stricter protective measures for workers in close contact with cows and milk products. Additionally, he calls for increased funding to better understand influenza in cows, as there is a significant amount of unknown information that needs to be rapidly addressed.