Structural and antigenic variation among diverse clade 2 H5N1 viruses.
Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-bindi...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/d83041ac521b487fb9b695b5850d36eb |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:d83041ac521b487fb9b695b5850d36eb |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:d83041ac521b487fb9b695b5850d36eb2021-11-18T08:53:27ZStructural and antigenic variation among diverse clade 2 H5N1 viruses.1932-620310.1371/journal.pone.0075209https://doaj.org/article/d83041ac521b487fb9b695b5850d36eb2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086467/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-binding properties of three H5N1 HPAI virus hemagglutinins, which were recently selected by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1), A/Hubei/1/2010 (Hubei10, clade 2.3.2.1) and A/Anhui/1/2005 (Anhui05, clade 2.3.4)]. These analyses revealed that antigenic diversity among these three isolates was restricted to changes in the size and charge of amino acid side chains at a handful of positions, spatially equivalent to the antigenic sites identified in H1 subtype viruses circulating among humans. All three of the H5N1 viruses analyzed in this study were responsible for fatal human infections, with the most recently-isolated strains, Hubei10 and Egypt10, containing multiple residues in the receptor-binding site of the HA, which were suspected to enhance mammalian transmission. However, glycan-binding analyses demonstrated a lack of binding to human α2-6-linked sialic acid receptor analogs for all three HAs, reinforcing the notion that receptor-binding specificity contributes only partially to transmissibility and pathogenesis of HPAI viruses and suggesting that changes in host specificity must be interpreted in the context of the host and environmental factors, as well as the virus as a whole. Together, our data reveal structural linkages with phylogenetic and antigenic analyses of recently emerged H5N1 virus clades and should assist in interpreting the significance of future changes in antigenic and receptor-binding properties.David A ShoreHua YangAmanda L BalishSamuel S ShepardPaul J CarneyJessie C ChangCharles T DavisRuben O DonisJulie M VillanuevaAlexander I KlimovJames StevensPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75209 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q David A Shore Hua Yang Amanda L Balish Samuel S Shepard Paul J Carney Jessie C Chang Charles T Davis Ruben O Donis Julie M Villanueva Alexander I Klimov James Stevens Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| description |
Antigenic variation among circulating H5N1 highly pathogenic avian influenza A viruses mandates the continuous production of strain-specific pre-pandemic vaccine candidates and represents a significant challenge for pandemic preparedness. Here we assessed the structural, antigenic and receptor-binding properties of three H5N1 HPAI virus hemagglutinins, which were recently selected by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1), A/Hubei/1/2010 (Hubei10, clade 2.3.2.1) and A/Anhui/1/2005 (Anhui05, clade 2.3.4)]. These analyses revealed that antigenic diversity among these three isolates was restricted to changes in the size and charge of amino acid side chains at a handful of positions, spatially equivalent to the antigenic sites identified in H1 subtype viruses circulating among humans. All three of the H5N1 viruses analyzed in this study were responsible for fatal human infections, with the most recently-isolated strains, Hubei10 and Egypt10, containing multiple residues in the receptor-binding site of the HA, which were suspected to enhance mammalian transmission. However, glycan-binding analyses demonstrated a lack of binding to human α2-6-linked sialic acid receptor analogs for all three HAs, reinforcing the notion that receptor-binding specificity contributes only partially to transmissibility and pathogenesis of HPAI viruses and suggesting that changes in host specificity must be interpreted in the context of the host and environmental factors, as well as the virus as a whole. Together, our data reveal structural linkages with phylogenetic and antigenic analyses of recently emerged H5N1 virus clades and should assist in interpreting the significance of future changes in antigenic and receptor-binding properties. |
| format |
article |
| author |
David A Shore Hua Yang Amanda L Balish Samuel S Shepard Paul J Carney Jessie C Chang Charles T Davis Ruben O Donis Julie M Villanueva Alexander I Klimov James Stevens |
| author_facet |
David A Shore Hua Yang Amanda L Balish Samuel S Shepard Paul J Carney Jessie C Chang Charles T Davis Ruben O Donis Julie M Villanueva Alexander I Klimov James Stevens |
| author_sort |
David A Shore |
| title |
Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| title_short |
Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| title_full |
Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| title_fullStr |
Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| title_full_unstemmed |
Structural and antigenic variation among diverse clade 2 H5N1 viruses. |
| title_sort |
structural and antigenic variation among diverse clade 2 h5n1 viruses. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/d83041ac521b487fb9b695b5850d36eb |
| work_keys_str_mv |
AT davidashore structuralandantigenicvariationamongdiverseclade2h5n1viruses AT huayang structuralandantigenicvariationamongdiverseclade2h5n1viruses AT amandalbalish structuralandantigenicvariationamongdiverseclade2h5n1viruses AT samuelsshepard structuralandantigenicvariationamongdiverseclade2h5n1viruses AT pauljcarney structuralandantigenicvariationamongdiverseclade2h5n1viruses AT jessiecchang structuralandantigenicvariationamongdiverseclade2h5n1viruses AT charlestdavis structuralandantigenicvariationamongdiverseclade2h5n1viruses AT rubenodonis structuralandantigenicvariationamongdiverseclade2h5n1viruses AT juliemvillanueva structuralandantigenicvariationamongdiverseclade2h5n1viruses AT alexanderiklimov structuralandantigenicvariationamongdiverseclade2h5n1viruses AT jamesstevens structuralandantigenicvariationamongdiverseclade2h5n1viruses |
| _version_ |
1718421232438738944 |