The mammary glands of cows abundantly display receptors for circulating avian H5 viruses

Abstract

Influenza A viruses (IAV) from the H5N1 2.3.4.4b clade are circulating in dairy farms in the United States of America, and goat infections have also been reported. These ruminants were presumed not to be hosts for IAVs. Previously, IAV-positive mammalian species were hunters and scavengers, possibly getting infected while feeding on infected birds. It is now presumed that H5N1 viruses that circulate in US dairy cattle transmit through a mammary gland route, in contrast to transmission by aerosols via the respiratory tract, although the latter cannot be excluded. The receptor display in the mammary and respiratory tract in cows for IAVs is unknown. Here, we used recombinant HA proteins representing current circulating and classical H5 viruses to determine the distribution of IAV receptors in the respiratory and mammary tract tissues of cows and goats. Most of the sialome of the cow and goat respiratory tract is lined with sialic acid modifications such as N-glycolyl and O-acetyl, which are not bound by IAV. Interestingly, the H5 protein representing the cow isolates bound significantly in the mammary gland, whereas classical H5 proteins failed to do so. Furthermore, whereas the 9-O-acetyl modification is prominent in all tissues tested, the 5-N-glycolyl modification is not, resulting in the display of receptors for avian IAV hemagglutinins. This could explain the high levels of virus found in these tissues and milk, adding supporting data to this possible virus transmission route.