N-linked sialic acid receptors

N-linked sialic acid receptors are glycan molecules displayed on the surface of mammalian cells that influenza viruses use as attachment points to initiate infection. The type of sialic acid receptor a flu strain prefers, and where in the body that receptor type is most abundant, determines which tissues the virus colonises and therefore what clinical signs it produces. This receptor tropism is what distinguishes a respiratory flu from an intestinal or, critically, an udder infection. A June 2026 Science Advances paper from the University of Pittsburgh, led by Suresh Kuchipudi, showed that H5N1 avian influenza preferentially binds N-linked sialic acid receptors that are abundant in bovine mammary gland tissue but near-absent in the cow respiratory tract. This receptor distribution explains why H5N1 presented as mastitis rather than flu across roughly 1,053 US dairy herds in 17 states, evading surveillance systems designed around respiratory illness.

Influenza receptor biology has long been understood in the context of human pandemic risk: H5N1 binds alpha-2,3-linked sialic acid (found in bird and bovine tissue) rather than alpha-2,6-linked sialic acid (dominant in human upper airways), which is one reason H5N1 does not yet spread easily between people. The Kuchipudi finding adds a second layer to this picture: within cattle, the receptor distribution is not uniform, meaning a virus can establish itself deeply in a specific tissue and circulate silently. The finding offers a receptor-mapping method to predict, ahead of the next spillover, which mammalian tissues a novel flu strain is most likely to colonise.

This udder-tropism mechanism is unrelated to the poultry-contact H5N1 cases now driving most of 2026's small rise in global human infections, in Cambodia and Bangladesh; that is a structurally distinct transmission route to the US dairy pathway this receptor finding explains.