The role of balanced haemagglutinin-neuraminidase activity in the genesis of transmissible neuraminidase inhibitor-resistant variants in seasonal and novel pandemic influenza A H1N1 viruses
HL Yen, JSM Peiris
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong
1. The H275Y mutation reduced neuraminidase enzyme activity, increased neuraminidase KM for 3’-sialyllactose or 6’-sialyllactose, decreased viral infectivity in mucin-secreting human airway epithelial cells, and attenuated pathogenicity in ferrets, when compared with its wild-type counterparts.
2. All H275Y variants of recombinant A(H1N1) pdm09 or seasonal H1N1 influenza viruses with different haemagglutinin-neuraminidase gene constellations were transmitted from inoculated ferrets to naïve direct contact or respiratory droplet contact ferrets, with the transmission efficiency minimally affected, when compared with their wild-type counterparts.
2. All H275Y variants of recombinant A(H1N1) pdm09 or seasonal H1N1 influenza viruses with different haemagglutinin-neuraminidase gene constellations were transmitted from inoculated ferrets to naïve direct contact or respiratory droplet contact ferrets, with the transmission efficiency minimally affected, when compared with their wild-type counterparts.