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Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses.
- Source :
-
Journal of virology [J Virol] 2017 Jan 03; Vol. 91 (2). Date of Electronic Publication: 2017 Jan 03 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Influenza A H3N2 variant [A(H3N2)v] viruses, which have caused human infections in the United States in recent years, originated from human seasonal H3N2 viruses that were introduced into North American swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating H3N2 strains. A reference A(H3N2)v virus, A/Minnesota/11/2010 (MN/10), and a seasonal H3N2 strain, A/Beijing/32/1992 (BJ/92), were chosen to determine the molecular basis for the antigenic difference between A(H3N2)v and the ancestral viruses. Viruses containing wild-type and mutant MN/10 or BJ/92 hemagglutinins (HAs) were constructed and probed for reactivity with ferret antisera against MN/10 and BJ/92 in hemagglutination inhibition assays. Among the amino acids that differ between the MN/10 and BJ/92 HAs, those in antigenic site A had little impact on the antigenic phenotype. Within antigenic site B, mutations at residues 156, 158, 189, and 193 of MN/10 HA to those in BJ/92 switched the MN/10 antigenic phenotype to that of BJ/92. Mutations at residues 156, 157, 158, 189, and 193 of BJ/92 HA to amino acids present in MN/10 were necessary for BJ/92 to become antigenically similar to MN/10. The HA amino acid substitutions responsible for switching the antigenic phenotype also impacted HA binding to sialyl receptors that are usually present in the human respiratory tract. Our study demonstrates that antigenic site B residues play a critical role in determining both the unique antigenic phenotype and receptor specificity of A(H3N2)v viruses, a finding that may facilitate future surveillance and risk assessment of novel influenza viruses.<br />Importance: Influenza A H3N2 variant [A(H3N2)v] viruses have caused hundreds of human infections in multiple states in the United States since 2009. Most cases have been children who had contact with swine in agricultural fairs. These viruses originated from human seasonal H3N2 viruses that were introduced into the U.S. swine population in the mid-1990s, but they are different from both these ancestral viruses and current circulating human seasonal H3N2 strains in terms of their antigenic characteristics as measured by hemagglutination inhibition (HI) assay. In this study, we identified amino acids in antigenic site B of the surface glycoprotein hemagglutinin (HA) that explain the antigenic difference between A(H3N2)v and the ancestral H3N2 strains. These amino acid mutations also alter binding to minor human-type glycans, suggesting that host adaptation may contribute to the selection of antigenically distinct H3N2 variants which pose a threat to public health.<br /> (Copyright © 2017 American Society for Microbiology.)
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Amino Acids
Animals
Antibodies, Viral immunology
Antigenic Variation
Antigens, Viral genetics
Antigens, Viral immunology
Epitopes genetics
Ferrets
Hemagglutinin Glycoproteins, Influenza Virus genetics
Hemagglutinin Glycoproteins, Influenza Virus metabolism
Humans
Mutation
Orthomyxoviridae Infections metabolism
Phenotype
Epitopes immunology
Hemagglutinin Glycoproteins, Influenza Virus immunology
Influenza A Virus, H3N2 Subtype physiology
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections virology
Receptors, Virus metabolism
Virus Attachment
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 91
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 27807224
- Full Text :
- https://doi.org/10.1128/JVI.01512-16