Mammary Gland Receptors Link Humans, Livestock to Avian Flu

Microscope images of a pig's mammary glands show flu receptors lighting up in orange and pruple.
Microscope-captured images of a mammary gland of a pig show the presence of influenza receptors. In the image on the left, receptors for avian influenza A are colored orange. In the image on the right, receptors for the type of influenza A that typically infects mammals are purple. Photos by Dr. Tyler Harm/Iowa State University.

Quick look

A new study led by Iowa State University researchers shows the mammary glands of pigs, sheep, goats, beef cattle, alpacas and humans are biologically suitable to be infected by H5N1 avian influenza, which has so far affected mostly poultry and dairy cattle.

AMES, Iowa - An ongoing outbreak of highly pathogenic avian influenza has affected more than 184 million domestic poultry since 2022 and, since making the leap to dairy cattle in spring 2024, more than 1,000 milking cow herds.

A new study led by Iowa State University researchers shows that the mammary glands of several other production animals - including pigs, sheep, goats, beef cattle and alpacas - are biologically suitable to harbor avian influenza, due to high levels of sialic acids.

"The main thing we wanted to understand in this study is whether there is potential for transmission among these other domestic mammals and humans, and it looks like there is," said Rahul Nelli, the study's lead author and a research assistant professor of veterinary diagnostic and production animal medicine.

Sialic acid, a sugar molecule found on the surface of many types of animal cells, provides an influenza virus the microscopic docking station it needs to infect a host cell, an entry point for attaching and invading. A study by many of the same researchers last year found that dairy cattle udders have high levels of sialic acid, which helped explain why the H5N1 avian influenza outbreak was able to spread rapidly among dairy herds.

In the study published Nov. 27 in the Journal of Dairy Science, a research team that includes scientists from the ISU College of Veterinary Medicine and the U.S. Department of Agriculture's National Animal Disease Center in Ames also found the same receptors in the mammary glands of the humans.

Only a few sporadic cases of H5N1 infection have been reported in the animals examined in the new study, but those species aren't being tested on a widespread basis, said Dr. Todd Bell, professor of veterinary pathology and a study co-author.

"If we don't look, we don't know," Bell said.

In dairy herds, H5N1 infections are causing sick cows to produce milk contaminated with the virus, prompting nationwide surveillance testing of raw cow milk samples by the USDA. Pasteurization kills influenza viruses, so store-bought milk is safe. But concerns about raw milk should extend to other mammalian livestock, Nelli said.

"Some people do consume the raw milk of these other animals," he said.

The presence of the virus in milk from infected cows has likely played a role in the H5N1 spreading and makes transmission to humans a bigger risk, Nelli said.

"If a virus in livestock is being spread by respiratory infections, few humans will be in close enough contact to catch it. But milk is an entirely different situation because it's transported into communities," he said.

All of the mammary gland tissues examined in the new study had sialic acid receptors preferred by both avian influenza and the seasonal influenza that circulates more readily among humans. The possibility of both types of viruses commingling and transmitting between different species heightens concerns about more dangerous adaptations emerging, Bell said. H5N1 has in the past had a fatality rate in humans of around 50%, though the 71 confirmed human infections during the current outbreak have led to just two deaths.

"We need to try to stay ahead of this so it doesn't have a chance to continue to replicate and potentially evolve into something even more troublesome," he said.

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