effect of d222g mutation in the hemagglutinin protein on receptor binding, pathogenesis and transmissibility of the 2009 pandemic h1n1 influenza virusd222g突变的影响血凝素蛋白受体结合,发病机理和2009年大流行h1n1流感病毒的传播性.pdfVIP

Effect of D222G Mutation in the Hemagglutinin Protein on Receptor Binding, Pathogenesis and Transmissibility of the 2009 Pandemic H1N1 Influenza Virus 1 2 2 1 1 1 Jessica A. Belser , Akila Jayaraman , Rahul Raman , Claudia Pappas , Hui Zeng , Nancy J. Cox , 1 2 1 Jacqueline M. Katz , Ram Sasisekharan , Terrence M. Tumpey * 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 2 Harvard-MIT Division of Health Sciences and Technology, Singapore-MIT Alliance for Research and Technology, Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose-dependent glycan array analysis with the D222G virus showed a modest reduction in the binding avidity to human-like (a2-6 sialylated glycan) receptors and an increase in the binding to a