Researchers have identified biological differences between the bovine mammary gland and respiratory tract that may explain why highly pathogenic avian influenza virus H5N1 primarily causes mastitis in dairy cattle rather than respiratory disease. The findings were published in Science Advances.
Since 2024, H5N1 clade 2.3.4.4b viruses have spread through dairy herds in the United States. Infected cattle typically develop inflammation of the mammary gland and shed large amounts of virus in milk, while respiratory symptoms are uncommon.
To understand this unusual pattern, researchers examined the receptors via which influenza viruses attach to cells. They compared tissues from the bovine mammary gland and trachea using a range of laboratory techniques, including glycan analysis, lectin histochemistry, virus-binding assays, and electron microscopy.
The study found that mammary tissue contains high levels of receptor structures that support influenza virus attachment. These receptors were widely distributed throughout the mammary gland, and H5N1 viruses showed strong binding to the tissue. Electron microscopy confirmed extensive viral attachment to mammary epithelial cells.
By contrast, the bovine trachea contained far fewer of the receptor structures needed for efficient viral attachment. Consistent with this finding, H5N1 viruses showed minimal binding to respiratory tissue.
According to the authors, these differences in receptor distribution help explain why H5N1 infection in cattle is concentrated in the mammary gland rather than the respiratory tract. The findings also suggest that simply detecting influenza receptors is not enough; the specific type and location of those receptors appear to influence which tissues the virus can infect.
The study provides a clearer understanding of the biology underlying H5N1 infection in dairy cattle. It also supports the importance of milk-based testing and surveillance, which have become key tools for detecting infection in affected herds. More broadly, the researchers suggest that detailed analysis of viral receptors could help improve assessments of influenza susceptibility in other animal species as H5N1 continues to spread to new hosts.
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