title: Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus.
abstract: We have analyzed the receptor binding profile of A(H1N1)pdm09 recombinant influenza viruses containing the amino acid substitution D222N which has been associated with a fatal case of infection. This mutation was investigated in conjunction with a secondary mutation, S185N. Using human tracheobronchial epithelial cells (HTBE), we found that single mutation D222N affects the binding and replication of the virus during initial stages of infection, with limited but preferred tropism to non-ciliated cells expressing α2,6-SA. However, in conjunction with the S185N change, the (D222N, S185N) virus shows a remarkable increase in binding and replication efficiency, with tropism for both ciliated and non-ciliated cells. Glycan microarray analysis demonstrated correlation between the binding profile and the cell tropism observed in the HTBE cells. These findings suggest that viruses with D222N required compensatory mutations such as S185N to maintain viral fitness, and in combination, affect the pathogenicity of the virus and the clinical outcome.
authors.affiliation: Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autonoma de Yucatan, Av. Itzaes #490×59, Centro, C. P., 97000 Merida, Yucatan, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Matos-Patrón
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Byrd-Leotis
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Steinhauer
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
authors.affiliation: Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autonoma de Yucatan, Av. Itzaes #490×59, Centro, C. P., 97000 Merida, Yucatan, Mexico. Electronic address: talavera@correo.uady.mx.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ayora-Talavera
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D056189:Viral Tropism; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins
keywords: A(H1N1)pdm09; Binding; Influenza; Mexico; Receptor