Intramammary infection of bovine H5N1 influenza virus in ferrets leads to transmission in suckling neonates

The spread of H5N1 clade 2.3.4.4b in dairy herds raises concerns about zoonotic transmission due to its high viral load in milk, a key contact point between livestock and humans. H5N1 clade 2.3.4.4b exhibits tropism for the mammary gland, with milk from infected animals containing high levels of infectious virus, posing potential risks to offspring via breastfeeding. Using a lactating ferret model, we demonstrate that mammary gland infection with bovine H5N1 transmits the virus to suckling kits, resulting in neonatal mortality. Viral RNA levels increased in milk and remained high in mammary tissue, with infected kits exhibiting elevated viral RNA in the oral and nasal cavities and feces. Additionally, we detected the H5N1 receptor, 2,3 sialic acid, in ferret and human mammary tissue. These data demonstrate that H5N1 clade 2.3.4.4b infection in lactating dams leads to mastitis-related disease and transmits to suckling pups, resulting in mortality among neonates.