As few as 10 virus particles of the H5N1 avian influenza strain that has caused hundreds of influenza outbreaks in U.S. dairy cows can cause infection in cows, a new study shows.
The study also suggests why this outbreak is perplexing to scientists, farmers, and livestock handlers who want to contain and prevent the disease, an effort likely complicated by the fact that the virus has an tropism for cows’ mammary glands rather than the respiratory tract.
Testing for cow-to-cow transmission through milking machines and feeding calves, and bird-to-cow transmission through sharing indoor air showed no results of disease spread.
Researchers continue to search for more answers, but for now the mystery of the infection persists, meaning scientists are still unable to provide evidence-based recommendations for practices to stop the spread.
“How it gets transmitted from cow to cow is a really important question. Whatever the milking method or the farming method, we need to understand whether there are ways to change it to limit cow-to-cow transmission, because we think spillover will happen again. It’s just a matter of time,” said lead author Andrew Bowman, professor of veterinary preventive medicine at The Ohio State University.
“And right now, there’s no good way to prevent that spillover or cow-to-cow transmission if it happens.”
This research recently nature communications.
Although highly pathogenic H5N1 avian influenza A viruses are associated with wild birds and poultry, a group of these viruses in clade 2.3.4.4b have been circulating globally in mammals since 2021 and were first reported in U.S. dairy cattle in March 2024.
To date, 1,053 outbreaks of the virus genotype first detected (B3.13) have been confirmed in dairy herds in 17 states and have been contained by a national milk testing strategy that halts the movement of herds producing milk where the virus is detected. Current federal data suggests a small number of confirmed cases of cattle in Idaho, Utah, and Texas.
All this work was done in response to the unprecedented spread of avian influenza in dairy cows. At first, we didn’t even know that cows could be infected with influenza, let alone that the mammary glands were involved. That in itself was a huge paradigm shift as it wasn’t the respiratory system. ”
Andrew Bowman, Professor of Veterinary Preventive Medicine, The Ohio State University
Bowman and his colleagues have been tracking the disease since it first appeared on dairy farms, and reported earlier this year that the virus had been detected in the retail milk supply. At that time, 36.3% of samples tested were positive for H5N1 particles.
“Pasteurization inactivates the virus, but once a cow is infected, it will produce milk with high virus titers for more than a week,” Bowman said.
These high virus titers or concentrations in milk are one of the results of current research, which involves testing the effects of varying levels of viral particle inoculation on the teats of individual cows with mammary glands.
The results showed that the lowest dose of 10 particles resulted in a productive infection, but fewer clinical symptoms and excretion of milk containing a higher concentration of virus particles than the higher dose.
“These are four separate mammary glands with a common blood supply, but in these small numbers of animals we don’t see much virus transfer between these mammary glands,” Bowman said. “I think this could be important in how sick a cow gets or doesn’t get because if one of the four glands is infected is different than if all four are severely infected.”
Several experiments aimed at identifying potential disease transmission routes.
Researchers transferred contaminated milking equipment directly from infected cows to healthy cows twice a day for 14 days. Although infected cows had clinical symptoms and their milk contained high numbers of virus particles, healthy cows exposed to contaminated equipment were unaffected and their milk was virus-free.
When calves were bottle-fed with high-viral titer milk from infected cows, virus detection and signs of inflammation in the calves were minimal, suggesting that transmission through feeding does not spread enough material to establish an infection.
Lactating cows given intranasal H5N1 virus did not become ill, and although the presence of viral RNA was minimal in nasal swabs and absent from milk, some respiratory tissues showed signs of an immune response compared to uninfected cows. These cows were housed with chickens that remained healthy after 17 days. Overall findings suggest that airborne transmission may be minimal, if it occurs at all.
The experiment was conducted in one of only six biosafety level 3 facilities in Japan that can house large animals. For airborne transmission in particular, Bowman said biocontainment conditions may have been too sterile and controlled airflow to resemble everyday farm life.
Also, conducting a limited number of tests on actual cows rather than surrogate models could become a “game of numbers,” he said. “About 20% of the cattle on the farm have been observed to develop clinical symptoms. Two infection trials may not be enough.
“I think we still need to look at milking equipment. The virus replicates to very high titers in the mammary glands and comes out at very high titers in the milk. We have a common contact device from cow to cow that contains high-risk material and transmits to high-risk tissues. I think the straight line between the two points shows that milking equipment is still a likely route of transmission between cows,” Bowman said.
“There’s still the bigger problem of transmission from wild birds to cattle. In waterfowl, it’s a pathogen that replicates in the intestines. How on earth does it get from the intestines of ducks to the mammary glands of cows? It’s a bit of a head-scratcher.”
This study was supported by the Center for Influenza Research and Response, funded by the National Institute of Allergy and Infectious Diseases.
Cody Warren and Scott Kenney of Ohio State University were co-lead authors. Other co-authors include Carolyn Lee, Natalie Tarbuck, Hannah Cochran, Bryant Foreman, Patricia Boley, Saroj Khatiwada, Alok Dhakal, Khadijat Adefai, Jennifer Shrock, Mohammad Javad Jahid, Tamongpan Raocharoensuk, Raksha Suresh, Olaytan Shekoni, Erica Stevens, and Sarah. Dolatiyabi, Christina Sanders, Elizabeth Orr, Devra Huey, Juliet Hanson, Kara Kopes, and Renukaladiya Ghrapura, all of Ohio; Jude Children’s Research Hospital.
The Plant and Animal Agrosecurity Research Facility is located on the Ohio State College of Food, Agricultural and Environmental Sciences Worcester campus.
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Reference magazines:
Lee, C. Others. (2026). Dairy cows infected with influenza A(H5N1) have been shown to have a low infectious dose and transmission barrier. nature communications. DOI: 10.1038/s41467-026-73490-6. https://www.nature.com/articles/s41467-026-73490-6
