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Bird flu viruses may infect mammary glands more commonly than thought

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The discovery of bird flu in dairy cow milk highlighted a previously overlooked target for the H5N1 virus: mammary glands. A new study suggests it’s not unique to cows.

An H5N1 virus isolated from an infected cow spread to the mammary glands of mice and some ferrets — common stand-ins to study flu infections in mammals — exposed to the virus directly in their noses, virologist Amie Eisfeld of the University of Wisconsin–Madison and colleagues report July 8 in Nature. A bird flu virus taken from an infected person in 2004 also made it to the mouse and ferret mammary glands. But additional experiments show that the virus isn’t very effective at spreading through the air.

These typically respiratory viruses are already known to infect a wide variety of other body tissues such as the brain (SN: 5/31/24). There had been previous hints that the virus could invade mammary tissue. A long-forgotten study from 1953 had shown that a different strain of bird flu could infect cow mammary glands. A separate study found that the 2009 pandemic virus could infect the tissue in ferrets.

The new study finds that the H5N1 virus currently circulating in U.S. cows also charts a path to mammary glands, suggesting that the tissue unique to mammals is a more common target for the virus than originally thought.

An ongoing H5N1 outbreak in U.S. cows has affected more than 135 dairy herds in 12 states. Some infected cattle have no symptoms, while others can develop a fever or tiredness, and their appetite and milk production may drop.

The virus has been detected in cow milk (SN: 4/25/24). The surface of cows’ mammary cells is covered in a ducklike protein that the bird flu virus can exploit to gain entry, researchers report in the July Emerging Infectious Diseases. Such infections might explain how the virus is spreading among cattle. It’s possible that contaminated milking equipment could carry virus from one cow’s udders to another, a separate group of researchers reported in the August Emerging Infectious Diseases.

Blue and purple dots are scattered around a microscopic image of cow mammary gland cells infected with bird flu
Tissue from cow mammary glands (shown) host a birdlike protein (purple) that bird flu viruses (blue) use to break inside cells.R.K. Nelli et al/Emerging Infectious Diseases 2024Tissue from cow mammary glands (shown) host a birdlike protein (purple) that bird flu viruses (blue) use to break inside cells.R.K. Nelli et al/Emerging Infectious Diseases 2024

Bird flu has also been detected in cows’ respiratory tracts. Yet despite lots of virus in that part of the body, there so far doesn’t seem to be much respiratory transmission, says virologist Richard Webby of St. Jude Children’s Research Hospital in Memphis, Tenn. It seems that “cows aren’t a really good host for this virus unless you go directly to the udder.”

In the new study, Eisfeld and colleagues exposed mice and ferrets to a variant of H5N1 taken from a cow in New Mexico to test whether the virus caused similar symptoms as in cows, and to better understand how the virus transmits.

In mice and ferrets, the virus spread to the lungs, as well as throughout the body to organs including the brain, intestines, kidney and heart. The virus also spread to the mammary glands of mice and some ferrets.

Infected female mice could transmit the virus to pups feeding on milk, but no transmission occurred through direct contact, the team found. Just one of four ferrets exposed to infected animals in a neighboring cage showed signs of infection, suggesting that the virus circulating among cows still isn’t very good at spreading through the air.

So what do these findings mean for people? The overall risk remains low, public health officials say. But farm workers in direct contact with animals have a higher risk for acquiring bird flu from cows than the public does. So far, four people in the United States have developed mild cases after working with infected animals. Anyone who consumes dairy is advised to avoid raw milk. But the milk on grocery store shelves remains safe to consume: On June 28, the U.S. Food and Drug Administration reported that a widely used pasteurization process effectively kills all H5N1 virus in milk.

One thing researchers are keeping a close eye on, though, is whether the virus is adapting in ways that could raise the risk of spread. Cows’ cells have entry portals for human flus as well as bird flus, which could make the animals mixing vessels that allow bird and human viruses to swap genes (SN: 5/14/24). That could create new versions of influenza that might better infect people.

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