THE ROLE OF INFLUENZA-A VIRUS HEMAGGLUTININ RESIDUE-226 AND RESIDUE-228 IN RECEPTOR SPECIFICITY AND HOST-RANGE RESTRICTION

Influenza A viruses can be isolated from a variety of animals, but the ir range of hosts is restricted. For example, human influenza viruses do not replicate in duck intestine, the major replication site of avia n viruses in ducks. Although amino acids at positions 226 and 228 of h emagglutinin (I-IA) of the H3 subtype are known to be important for th is host range restriction, the contributions of specific amino acids a t these positions to restriction were not known. Here, me address this issue by generating Has with site-specific mutations of a human virus that contain different amino acid residues at these positions. We als o let ducks select replication-competent viruses from a replication-in competent virus containing a human virus HA by inoculating animals wit h 10(10.5) 50% egg infectious dose of the latter virus and identified a mutation in the HA. Our results showed that the Ser-to-Gly mutation at position 228, in addition to the Leu-to Gln mutation at position 22 6 of the HA of the H3 subtype, is critical for human virus HA to suppo rt virus replication in duck intestine.