Identification of a key amino acid in hemagglutinin that increases human-type receptor binding and transmission of an H6N2 avian influenza virus

Binding exclusively to human-type receptors is a prerequisite for avian influenza viruses to transmit from human to human. We previously reported that 34% of H6 avian influenza viruses recognize the human-type receptor, but their affinity for the avian-type receptor remains higher than that for the human-type receptor. Here, we found that a single amino acid change from glutamine to leucine at position 226 of hemagglutinin caused a switch in receptor-binding preference from avian-type to human-type receptors and rendered A/chicken/Guangdong/S1312/2010(H6N2) capable of respiratory droplet transmission in guinea pigs.