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Bird Flu in the Barnyard
On most farms, fences are built to keep animals contained and to protect herds and crops. Beyond simply marking boundaries, these structures help maintain order and organization across the farm, guiding the movement of livestock and the layout of fields.
However, while fences shape the physical landscape, they provide no protection against invisible threats: pathogens that can spread disease, harm livestock, or contaminate food.
Interspecies transmission spillover occurs when a pathogen jumps from one species to another, crossing biological barriers that typically keep infections contained. When a pathogen crosses that invisible boundary, the consequences can extend far beyond a single host.
Spillover is rarely a singular event. Viruses are inherently unstable and constantly evolving, traits that make them uniquely suited to adapt to different environments, exploit new hosts, and capitalize on opportunities for transmission. As these pathogens circulate into new hosts, each infection presents another chance for mutation, increasing the possibility of increased pathogenicity, interspecies spread, and wider outbreaks.
In March 2024, highly pathogenic avian influenza A (H5N1), long recognized as a threat to poultry and wild birds, was detected in dairy cattle. This unexpected shift prompted urgent scientific investigation into how the virus behaves in mammals.
St. Jude scientists are working to understand these transitions in real time and clarify how the virus moves across species, adapts within new hosts, and the risk to humans at the intersection of veterinary and public health.
Assessing pandemic potential
Traditionally, influenza viruses are classified as avian or mammalian based on their host range and biology. The spillover of an avian influenza virus into mammalian livestock causes concern that continued circulation in these animals could drive genetic changes associated with increased human infectivity. This pattern has been observed most clearly in the 2009 H1N1 influenza pandemic, which emerged in humans after prolonged circulation and genetic reassortment in swine, as well as pandemics in 1957 and 1968 that involved avian influenza strains moving between species, and acquiring adaptations that enhanced their ability to infect humans. Researchers need to understand what kind of effects might occur as a result of this current outbreak.
“When the outbreak in cows first appeared, no one really knew what to expect — after all, cows aren’t typical hosts for influenza A,” said Richard Webby, PhD, Department of Host-Microbe Interactions. “The fear is that once it’s in a mammal, continued transmission could push it closer to becoming a threat to humans.”
When the outbreak in cows first appeared, no one really knew what to expect — after all, cows aren’t typical hosts for influenza A. The fear is that once it’s in a mammal, continued transmission could push it closer to becoming a threat to humans.
Department of Host-Microbe Interactions
In a study published in Nature Communications, Webby and his team analyzed a panel of H5N1 viruses isolated from dairy cows to assess their potential risk of infecting humans.
They found the viruses had more molecular and biological features in common with bird flu viruses than human flu viruses, and that, fortunately, the virus was not under tremendous pressure to mutate in the cow udders — the tissue where most virus was found. They also found that the viruses from cows could not transmit through the air between mammals, though transmission to humans by close contact with infected dairy cattle is possible.
“While the overall population risk remains low for now, the greatest concern is for people who have close, direct contact with infected animals or who may be exposed through consumption of contaminated, unpasteurized milk,” said Webby. “We do need to remain vigilant for human infections, as each new person infected is another chance for this virus to mutate to better infect and spread among us.”
The researchers further showed that the virus did not exhibit evidence of resistance markers to current antiviral medications. However, there does appear to be a slightly higher baseline resistance to some drugs compared to others, which may mean a somewhat higher dose is needed for effective treatment.
Risk, route, response
While the overall pandemic risk remains low, the spread of the virus into dairy cattle has shifted the focus to those at risk of direct exposure. Because host biology can shape how influenza behaves, it raises important questions about which antiviral medications will be most effective and what role the route of transmission plays in caring for and treating exposed individuals.
“The introduction of the virus into dairy cattle has created an entirely new potential route of exposure,” explained Webby. “We now have to consider risks such as splashes to the eye in people working in milking parlors, the possibility of consuming contaminated milk, and even aerosolized exposure in these environments.”
In response to these emerging risks, Webby and his team designed a study to model real-world exposure scenarios. The researchers studied exposure routes that included the eyes, mouth, and nose, which are the most common ways to become infected with the virus. By modeling these different routes, they aimed to better understand the virus’s threat to human health and how two Food & Drug Administration (FDA)–approved flu antiviral drugs performed depending on the route of transmission.
This study, published in Nature Microbiology, found that the route of infection, whether through the eyes, nose, or mouth, significantly impacts a treatment’s effectiveness. The oral route, which mimics the consumption of contaminated raw cow’s milk, resulted in the most severe and difficult-to-treat infections. The drug baloxavir produced a greater reduction in viral levels than oseltamivir, although neither was consistently effective across all routes of exposure.
This variability suggests that current antiviral strategies may need to be specifically tailored rather than relying on a single standardized treatment approach.
“Our evidence suggests that it is likely going to be hard to treat people severely infected with this bovine H5N1 bird flu strain,” said Webby. “Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers’ exposures may be the most effective interventions.”
Ensuring food safety
This understanding about the route of exposure raises important questions about broader public health and food safety, particularly the safety of milk consumption given current processing methods. Pasteurization, heating milk to a specific temperature for a set time, inactivates harmful pathogens, safeguarding consumers from contaminated milk. However, not all milk is pasteurized, and although pasteurization inactivates infectious viruses, inactivated proteins and genetic material from H5N1 influenza have been reported in over 30% of commercial milk.
Researchers were also interested in how repeated oral exposure of these viral components might impact host immunity, including the potential to lead to or disrupt oral tolerance. Oral tolerance is the mechanism that teaches the immune system to ignore innocuous antigens, such as harmless food proteins, a process that normally protects us from misdirected immunity. Because the immunologic effects of ingesting viral remnants are not well understood, researchers questioned whether ingesting milk containing viral fragments could induce tolerance to the virus and lead to altered immune responses to subsequent viral infection.
In a study published in Science Advances, Stacey Schultz-Cherry, PhD, Department of Host-Microbe Interactions, investigated the effect of exposure to these viral fragments and their impact on immune responses and influence on disease onset or susceptibility to subsequent infection. “We found that consuming pasteurized milk multiple times, even if it has inactivated H5N1 virus, poses minimal health risks,” said Schultz-Cherry. The researchers observed no benefit or detriment to subsequent influenza infection with regard to pasteurized milk’s effect on the immune system.
The work confirms that current food safety methods are likely protecting humans from the H5N1 virus in milk. However, without pasteurization, the researchers did observe that infected milk was still very pathogenic in their model.
“It’s reassuring to find that these inactivated H5N1 viral components in pasteurized milk present minimal health risks and don’t alter flu immunity,” Schultz-Cherry said. “However, we also reaffirmed that consuming unpasteurized milk can expose people to this potentially dangerous infectious agent. We must continue to watch this virus and mitigate its risk of spilling over into the human population.”
It’s reassuring to find that these inactivated H5N1 viral components in pasteurized milk present minimal health risks and don’t alter flu immunity. However, we also reaffirmed that consuming unpasteurized milk can expose people to this potentially dangerous infectious agent.
Department of Host-Microbe Interactions
When viruses cross the fence
As scientists continue to study H5N1 in dairy cattle and its potential impact on humans, their findings guide efforts to understand and mitigate emerging risks. By examining how the virus spreads, mutates, and responds to antiviral treatments, St. Jude researchers are building the foundation to protect those most at risk and to anticipate future threats.
Their work highlights the importance of careful monitoring and study of these viruses, prevention, safe handling of livestock, and food safety measures, ensuring that public health strategies stay one step ahead of a virus that crosses the fence from animals to humans.