Recognition of N-glycolylneuraminic acid linked to galactose by the alpha 2,3 linkage is associated with intestinal replication of influenza A virus in ducks

The hemagglutinin (IU) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gin mutat ion at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, wit h all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in d ucks. To understand the molecular basis of this change in host range restri ction, we investigated the receptor specificity of duck influenza viruses a s well as of human-duck virus reassortants. The results indicate that the r ecognition of a glycoconjugate moiety possessing N-glycolneuramic acid (Neu Gc) linked to galactose by the alpha 2,3 linkage (NeuGc alpha 2,3Gal) is as sociated with viral replication in duck intestine. Immunofluorescence assay s with NeuGc alpha 2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together wi th biochemical evidence of NeuGc in crypt cells, correlated exactly with th e ability of the virus to replicate in duck colon. These results suggest th at recognition of the NeuGc alpha 2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.