Effects of the Q223R mutation in the hemagglutinin (HA) of egg-adapted pandemic 2009 (H1N1) influenza A virus on virus growth and binding of HA to human- and avian-type cell receptors

Abstract

The 2009 swine-origin influenza A virus (H1N1) and its initial reassortant vaccine strains did not grow well in embryonated eggs. The glutamine to arginine mutation at the amino acid position 223 (Q223R) of the hemagglutinin (HA) gene is the major mutation previously found in egg-adapted 2009 H1N1 strains and shown to enhance viral growth in embryonated eggs. However, the effect of this mutation on the receptor-binding preference had not been directly demonstrated. In this study, the Q223R mutation was shown to change the viral HA binding preference from the human-type receptor, α2,6-linked sialic acid, to the avian-type receptor, α2,3-linked sialic acid; and to enhance the viral growth in embryonated eggs but not in cell culture.