Dairy cow- and avian-origin clade 2.3.4.4b H5N1 induce severe mastitis in lactating goats and transmission to suckling goats

The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has led to unprecedented spillover and spread among US dairy cows, raising concerns about transmission to other ruminants. We inoculated two groups of lactating goats via intramammary and respiratory routes with Cow-H5N1 (genotype B3.13) or avian-H5N1 (genotype B1.2) virus. Both groups developed severe clinical mastitis and shed viruses in milk, resulting in transmission to suckling kids. Viral RNA was detected in nasal and oral swabs and various tissues, and virus-neutralizing antibodies were present in serum, milk, and bronchoalveolar lavage fluid. In vitro, both viruses replicated efficiently in goat respiratory and mammary epithelial cells. Mammary tissue expresses both α2,3- and α2,6-linked sialic acid receptors. These findings demonstrate that goats are highly susceptible to H5N1 infection, with mammary tropism facilitating transmission to offspring, and underscore the need for increased surveillance in ruminant livestock.