Biol. Pharm. Bull. 28(3) 399—408 (2005)

In 1942, Hirst found that chicken erythrocytes were agglutinated when the cells were mixed with influenza virus at 4 °C and that the agglutinated cells were eluted spontaneously when the temperature was raised to 37 °C. The washed cells once eluted from the virus were never agglutinated by a newly added influenza virus. This phenomenon made him to introduce a new concept that a specific receptor for the influenza virus is present in the erythrocyte membrane and binds to the viral hemagglutinin at 4 °C and also that the virus has an enzyme that destroys the receptor on the host cell surface at 37 °C. A receptor-destroying enzyme was found in the culture filtrate of Vibrio cholerae by Burnet’s group, and was later identified as sialidase by Gottschalk’s group. Influenza virus hemagglutinin and sialidase have different functions in viral infection, but both molecules commonly recognize the glycoconjugates that contain sialic acid, and the mechanisms by which sialo-sugar chains are recognized by influenza viruses have therefore been a very interesting target as a model to study the receptor and biological ligand interaction that is mediated by sialo-sugar chains in cell membranes.