6/19/2026
New Pitt research provides the first mechanistic explanation for H5N1's surprising behavior in dairy cattle, and offers a biological framework to predict where the virus will strike next.
PITTSBURGH — When H5N1 bird flu began spreading through U.S. dairy cattle herds in March 2024, it went unrecognized for weeks — because in cows, it looked nothing like bird flu had ever looked before. Now, for the first time, University of Pittsburgh School of Public Health researchers have explained why.
A study published June 19, 2026, in Science Advances reveals that H5N1 — a highly pathogenic avian influenza A virus that has spread to more than 100 bird and mammal species globally — exploits a specific molecular receptor that is abundant in cow udders but nearly absent in cow airways. That biological fact explains why the virus caused devastating udder infections in cattle rather than the respiratory disease seen in other mammals.
The disease initially appeared along the Texas Panhandle as severe, treatment-resistant mastitis — a painful inflammatory condition affecting mammary tissue. Veterinarians, expecting bacterial causes, were not looking for bird flu.
"Mastitis is a classic disease in milk-production animals, and veterinarians were dutifully looking to all the usual suspects for the source, like bacterial pathogens," said senior author Suresh Kuchipudi, Ph.D., chair of Infectious Diseases and Microbiology at Pitt Public Health. "When the real culprit turned out to be bird flu, everyone in the field was caught completely by surprise. We hadn't even remotely considered that cattle could be a host for H5N1."
In the weeks before the virus was identified, it moved from herd to herd — contaminating animals and their environments.
What the Study Found
The key findings:
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N-linked sialic acid receptors — a specific subtype of glycan, or sugar-based molecule —act as the virus's entry point into cells. They are virtually absent in the airway tissue of dairy cattle but are highly abundant in udder tissue.
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This distribution explains why H5N1 causes severe mastitis in cows rather than the respiratory illness seen in other mammals.
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A multimodal glycomics framework — combining molecular binding assays, immunofluorescence staining and ultra-high-resolution imaging — can now be used to screen any species or tissue for H5N1 susceptibility before an outbreak occurs.
Earlier studies had detected glycan receptors in cow respiratory tissue but could not explain why cows were not developing respiratory infections. The Pitt team, collaborating with Lauren E. Pepi, Ph.D., a glycomics expert at Harvard Medical School, used higher-resolution techniques to map receptor architecture at the cellular level — revealing distinctions that prior methods had missed. Glycomics is the comprehensive study of all glycan structures in a biological system.
"Glycan biology is very complex," Kuchipudi said. "We realized that, to understand what was really going on, we would need to use more sensitive, high-resolution technologies and map the fine-grained receptor architecture that enables the virus to bind to cells."
A Tool for Predicting the Next Surprise
The research moves directly from molecular biology to public health practice. By mapping receptor distribution across species and tissues, scientists can now preemptively assess not just whether H5N1 could infect a new host — but where in the body it would cause disease and what symptoms it would produce.
"We can preemptively screen different species and different tissues within them for susceptibility," Kuchipudi said. "Would they exhibit respiratory symptoms? Would they show only mastitis, as in cows? Or would they show neurological disease, as our team has shown in cats? The lessons learned could potentially help prevent us from being caught by surprise again."
Infected cows shed large quantities of virus into milk, raising occupational exposure concerns for farm workers — a population that often faces barriers to occupational health services and whose exposure risk can go underreported. Pasteurization effectively inactivates H5N1, making commercially pasteurized dairy products safe to consume. Public health authorities advise against drinking raw, unpasteurized milk.
The findings have direct implications for veterinary diagnostic protocols and pandemic preparedness. By providing a validated biological basis for predicting tissue-level susceptibility, the research could shorten the critical gap between a novel H5N1 host jump and its correct diagnosis — the gap that cost weeks of undetected spread when the virus first appeared in U.S. dairy herds. The approach reflects a One Health perspective — the recognition that human, animal and environmental health are deeply interconnected.
Frequently Asked Questions
Q: Why did H5N1 bird flu cause udder infections in cows instead of lung infections?
A: University of Pittsburgh researchers found that a specific receptor type — N-linked sialic acid receptors — that H5N1 can bind to is nearly absent in cow lung tissue but abundant in udder tissue. That receptor distribution steered the virus to the mammary glands, producing severe mastitis rather than respiratory disease.
Q: How can this research help prepare for future bird flu outbreaks in new animals?
A: The Pitt team developed a glycomics-based screening framework that can assess any species and its tissues for H5N1 susceptibility — predicting not just whether infection is possible, but where in the body it would occur and what symptoms it would cause. That could help health officials identify and respond to new host jumps before weeks of undetected spread occur.
Q: Is milk from dairy cows safe to drink?
A: Commercially pasteurized milk is safe. Pasteurization effectively inactivates H5N1 and other influenza viruses. Public health authorities advise against consuming raw, unpasteurized milk, which may carry active virus.
Additional Resources
- Published study: “Receptor Basis of Unusual Tissue Tropism of Avian Influenza H5N1 Clade 2.3.4.4b Virus in Cattle” in Science Advances
- EurekAlert! release: “How H5N1 Bird Flu Hid Unrecognized for Weeks in Dairy Cattle”
- Press contact: Elaine Vitone | UPMC Media Relations
- World Health Organization resources: “Avian influenza”
- Related Pitt coverage: “Pennsylvania One Health Consortium”
- Related Pitt coverage: “Kuchipudi lab takes aim at bird flu, emerging diseases”
- Related UPMC coverage: “Bird flu stays stable on milking equipment for at least one hour”
- Multimedia: Dr. Suresh Kuchipudi head shot
- Social media: University of Pittsburgh School of Public Health | LinkedIn
Authors and Funding
Authors: Surabhi Srinivas, M.S., Shubhada K. Chothe, Ph.D., Santhamani Ramasamy, Ph.D., Sougat Misra, Ph.D., Noel Chandan Nallipogu, M.D., M.P.H., and Lindsey LaBella, all of Pitt; Yin-Ting Yeh, Ph.D., of Pennsylvania State University; May Wang, B.S., of Harvard University; Lauren E. Pepi, Ph.D., of Harvard Medical School; and Heidi L. Pecoraro, Ph.D., and Brett T. Webb, Ph.D., of North Dakota State University. Suresh Kuchipudi, Ph.D., of the University of Pittsburgh School of Public Health, was senior author.
Funding and Disclosures: This research was supported by Pitt Public Health and the U.S. Department of Agriculture's National Institute of Food and Agriculture (FP00039373/AWD00010780).
