Cargando…
Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses
Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating vi...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825936/ https://www.ncbi.nlm.nih.gov/pubmed/27057693 http://dx.doi.org/10.1371/journal.ppat.1005526 |
_version_ | 1782426270303256576 |
---|---|
author | Harvey, William T. Benton, Donald J. Gregory, Victoria Hall, James P. J. Daniels, Rodney S. Bedford, Trevor Haydon, Daniel T. Hay, Alan J. McCauley, John W. Reeve, Richard |
author_facet | Harvey, William T. Benton, Donald J. Gregory, Victoria Hall, James P. J. Daniels, Rodney S. Bedford, Trevor Haydon, Daniel T. Hay, Alan J. McCauley, John W. Reeve, Richard |
author_sort | Harvey, William T. |
collection | PubMed |
description | Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. |
format | Online Article Text |
id | pubmed-4825936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48259362016-04-22 Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses Harvey, William T. Benton, Donald J. Gregory, Victoria Hall, James P. J. Daniels, Rodney S. Bedford, Trevor Haydon, Daniel T. Hay, Alan J. McCauley, John W. Reeve, Richard PLoS Pathog Research Article Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. Public Library of Science 2016-04-08 /pmc/articles/PMC4825936/ /pubmed/27057693 http://dx.doi.org/10.1371/journal.ppat.1005526 Text en © 2016 Harvey et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Harvey, William T. Benton, Donald J. Gregory, Victoria Hall, James P. J. Daniels, Rodney S. Bedford, Trevor Haydon, Daniel T. Hay, Alan J. McCauley, John W. Reeve, Richard Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title | Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title_full | Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title_fullStr | Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title_full_unstemmed | Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title_short | Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses |
title_sort | identification of low- and high-impact hemagglutinin amino acid substitutions that drive antigenic drift of influenza a(h1n1) viruses |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825936/ https://www.ncbi.nlm.nih.gov/pubmed/27057693 http://dx.doi.org/10.1371/journal.ppat.1005526 |
work_keys_str_mv | AT harveywilliamt identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT bentondonaldj identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT gregoryvictoria identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT halljamespj identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT danielsrodneys identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT bedfordtrevor identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT haydondanielt identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT hayalanj identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT mccauleyjohnw identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses AT reeverichard identificationoflowandhighimpacthemagglutininaminoacidsubstitutionsthatdriveantigenicdriftofinfluenzaah1n1viruses |