Hemagglutinin Traits Determine Transmission of Avian A/H10N7 Influenza Virus between Mammals

In 2014, an outbreak of avian A/H10N7 influenza virus occurred among seals along North-European coastal waters, significantly impacting seal populations. Here, we examine the cross-species transmission and mammalian adaptation of this influenza A virus, revealing changes in the hemagglutinin surface protein that increase stability and receptor binding. The seal A/H10N7 virus was aerosol or respiratory droplet transmissible between ferrets. Compared with avian H10 hemagglutinin, seal H10 hemagglutinin showed stronger binding to the human-type sialic acid receptor, with preferential binding to α2,6-linked sialic acids on long extended branches. In X-ray structures, changes in the 220-loop of the receptor-binding pocket caused similar interactions with human receptor as seen for pandemic strains. Two substitutions made seal H10 hemagglutinin more stable than avian H10 hemagglutinin and similar to human hemagglutinin. Consequently, identification of avian-origin influenza viruses across mammals appears critical to detect influenza A viruses posing a major threat to humans and other mammals. [Display omitted] •Adaptation to seals led to transmission of avian A/H10N7 virus between mammals•Three substitutions in HA altered receptor-binding preference and changed stability•Receptor-binding specificity substitutions are located in the 220-loop of the HA•A/H10N7 mammal transmission requirements resemble those for A/H5N1 and other viruses Herfst et al. investigated an outbreak in seals caused by an H10N7 influenza virus. In laboratory experiments, this virus was transmissible via the air between ferrets, similar to human influenza viruses. This was caused by mutations that changed the binding pattern and stability of the influenza virus hemagglutinin surface protein.