When H5N1 avian influenza first started infecting cattle in the United States in early 2024, diagnosis was difficult because the disease looked very different in cattle. Rather than affecting the lungs as it does in other mammals, the H5N1 virus caused a severe infection in the cow’s udder, largely sparing the lungs.
A study by researchers at the University of Pittsburgh School of Public Health was published today. scientific progress describe for the first time the mechanisms behind this unique new guise of H5N1, which currently affects more than 100 bird and mammal species worldwide. The research also establishes a new method to help scientists spot the next surprising move in bird flu more quickly, saving precious time to implement public health measures to stop its spread.
The disease first appeared in dairy cows along the Texas Panhandle as a stubborn case of severe necrotizing mastitis, a painful inflammatory condition that damages mammary gland tissue.
Mastitis is a typical disease of milk-producing animals, and veterinarians were dutifully on the lookout for any disease with a suspected source, including bacterial pathogens. Everyone at the scene was completely surprised when the real culprit turned out to be avian influenza. We never thought in the slightest that cows could be a host for H5N1. ”
Dr. Suresh Kuchipudi, Senior Author, Chief of Infectious Diseases and Microbiology, Pitt Public Health Service
In the weeks before the virus was identified, it moved from herd to herd, sickening cattle and contaminating the environment.
“When a cow is infected, a large amount of virus is shed in the milk,” Kuchipudi said. “This has raised concerns about occupational risks for farm workers. There has also been a practice of feeding raw milk to pets such as cats, which has resulted in cat deaths, which we previously investigated.” He stressed that, fortunately, pasteurization is effective in killing the virus, and stressed the importance of avoiding raw milk.
Kuchipudi has spent his entire career studying influenza viruses, with a particular focus on how receptor biology determines which species and which tissues they are likely to infect. Typically, such studies involve staining cells for the presence of receptors (a subset of sugar-based molecules known as glycans) that are known to function in a keyhole relationship with influenza.
In earlier studies by other groups, such experiments suggested that glycan receptors associated with influenza are present in cows’ noses, tracheas, and lungs. Nevertheless, the fact that the animals did not develop respiratory infections told the team there was more to this story.
“Glycan biology is very complex,” Kuchipudi says. “We realized that to understand what was actually going on, we needed to use more innovative techniques and map out the detailed structures that allow the virus to bind to cells.” Kuchipudi collaborated on the study with Dr. Loren E. Pepi of Harvard Medical School, an expert in a methodology that comprehensively catalogs the entire glycan structure called glycomics.
Using a multimodal approach that combines binding experiments, staining techniques, and ultra-high-resolution imaging, the research team revealed that not all glycan receptors function in the same way in animals infected with avian influenza. Only certain subtypes known as N-linked sialic acid receptors can bind H5N1. These receptors are virtually absent in cow airway tissue, but are prevalent in the udder, making it “a perfect breeding ground for the virus,” Kuchipudi said.
This study provides a framework that could potentially allow other scientists to predict not only whether but also how H5N1 can jump to new hosts.
“We can pre-screen the susceptibility of different species and different tissues within them,” Kuchipudi said. “For example, will they show respiratory symptoms? Will they show only mastitis, like cows? Or will they show neurological disease, as our team has shown in cats? The lessons learned could help us avoid being caught by surprise again.”
Other authors of the study are Surabhi Srinivas, Ph.D., Shubhada K. Chothe, Ph.D., Santhamani Ramasamy, Ph.D., Sougat Misra, Ph.D., Noel Chandan Nallipogu, MD, MPH, Lindsey LaBella, all of Pitt. Yingting Yeh, Ph.D., Penn State University; Mei Wang, Bachelor of Science, Harvard University; Dr. Heidi L. Pecoraro and Dr. Brett T. Webb of North Dakota State University;
This research was supported by Pitt Public Health and the USDA National Institute of Food and Agriculture (FP00039373/AWD00010780).
sauce:
Reference magazines:
Srinivas, S. others. (2026) Receptor basis of aberrant tissue tropism of avian influenza H5N1 clade 2.3.4.4b virus in cattle. scientific progress. DOI: 10.1126/sciadv.aea2068. https://www.science.org/doi/10.1126/sciadv.aea2068
