Journal Article

Three mutations switch H7N9 influenza to human-type receptor specificity

Thompson, Andrew J., Peng, Wenjie, Grant, Oliver C., Wilson, Ian A., Ambepitiya Wickramasinghe, Iresha N., Sanders, Rogier W., de la Pena, Alba T. Torrents, de Vries, Robert P., Bouwman, Kim M., McBride, Ryan, Zhu, Xueyong, van Breemen, Marielle J., Woods, Robert J., Yu, Wenli, Paulson, James C., de Haan, Cornelis A. M., Verheije, Monique H.

2017

Overview

The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 60 APPLIED LIFE SCIENCES / Amino Acid Sequence / Amino acids / Analysis / Animals / BASIC BIOLOGICAL SCIENCES / Biology / Biology and life sciences / Carbohydrates / chickens / China / Departments / Disease transmission / Epidemics / Epithelial cells / Genetic aspects / Grants / H1N1 / H5N1 / H7N9 / Health aspects / Hemagglutinin Glycoproteins, Influenza Virus - chemistry / Hemagglutinin Glycoproteins, Influenza Virus - genetics / Hemagglutinin Glycoproteins, Influenza Virus - metabolism / Hemagglutinins / Host Specificity / Humans / Immunology / Incidence / Influenza / Influenza A virus / Influenza A Virus, H3N2 Subtype - chemistry / Influenza A Virus, H3N2 Subtype - genetics / Influenza A Virus, H3N2 Subtype - metabolism / Influenza A Virus, H7N9 Subtype - chemistry / Influenza A Virus, H7N9 Subtype - genetics / Influenza A Virus, H7N9 Subtype - metabolism / Influenza in Birds - genetics / Influenza in Birds - metabolism / Influenza in Birds - virology / Influenza, Human - genetics / Influenza, Human - metabolism / Influenza, Human - virology / Lectins / Medicine and health sciences / microbial mutation / Molecular Sequence Data / Mutation / Outbreaks / Pandemics / Pathology / Poultry / Poultry Diseases - genetics / Poultry Diseases - metabolism / Poultry Diseases - virology / Prevention / Protein Binding / receptor binding assays / Receptors / Receptors, Virus - genetics / Receptors, Virus - metabolism / Research and Analysis Methods / Risk factors / Sequence Alignment / Swine influenza / Trachea / Veterinary medicine / Virology / Viruses