2.50
Hdl Handle:
http://hdl.handle.net/10033/620914
Title:
Determination of antigenicity-altering patches on the major surface protein of human influenza A/H3N2 viruses.
Authors:
Kratsch, Christina; Klingen, Thorsten R; Mümken, Linda; Steinbrück, Lars; McHardy, Alice Carolyn
Abstract:
Human influenza viruses are rapidly evolving RNA viruses that cause short-term respiratory infections with substantial morbidity and mortality in annual epidemics. Uncovering the general principles of viral coevolution with human hosts is important for pathogen surveillance and vaccine design. Protein regions are an appropriate model for the interactions between two macromolecules, but the currently used epitope definition for the major antigen of influenza viruses, namely hemagglutinin, is very broad. Here, we combined genetic, evolutionary, antigenic, and structural information to determine the most relevant regions of the hemagglutinin of human influenza A/H3N2 viruses for interaction with human immunoglobulins. We estimated the antigenic weights of amino acid changes at individual sites from hemagglutination inhibition data using antigenic tree inference followed by spatial clustering of antigenicity-altering protein sites on the protein structure. This approach determined six relevant areas (patches) for antigenic variation that had a key role in the past antigenic evolution of the viruses. Previous transitions between successive predominating antigenic types of H3N2 viruses always included amino acid changes in either the first or second antigenic patch. Interestingly, there was only partial overlap between the antigenic patches and the patches under strong positive selection. Therefore, besides alterations of antigenicity, other interactions with the host may shape the evolution of human influenza A/H3N2 viruses.
Affiliation:
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
Citation:
Determination of antigenicity-altering patches on the major surface protein of human influenza A/H3N2 viruses. 2016, 2 (1):vev025 Virus Evol
Journal:
Virus evolution
Issue Date:
Jan-2016
URI:
http://hdl.handle.net/10033/620914
DOI:
10.1093/ve/vev025
PubMed ID:
27774294
Type:
Article
Language:
en
Appears in Collections:
publications of the research group bioinformatics in infection research ([BRICS] BIFO)

Full metadata record

DC FieldValue Language
dc.contributor.authorKratsch, Christinaen
dc.contributor.authorKlingen, Thorsten Ren
dc.contributor.authorMümken, Lindaen
dc.contributor.authorSteinbrück, Larsen
dc.contributor.authorMcHardy, Alice Carolynen
dc.date.accessioned2017-05-09T14:07:16Z-
dc.date.available2017-05-09T14:07:16Z-
dc.date.issued2016-01-
dc.identifier.citationDetermination of antigenicity-altering patches on the major surface protein of human influenza A/H3N2 viruses. 2016, 2 (1):vev025 Virus Evolen
dc.identifier.pmid27774294-
dc.identifier.doi10.1093/ve/vev025-
dc.identifier.urihttp://hdl.handle.net/10033/620914-
dc.description.abstractHuman influenza viruses are rapidly evolving RNA viruses that cause short-term respiratory infections with substantial morbidity and mortality in annual epidemics. Uncovering the general principles of viral coevolution with human hosts is important for pathogen surveillance and vaccine design. Protein regions are an appropriate model for the interactions between two macromolecules, but the currently used epitope definition for the major antigen of influenza viruses, namely hemagglutinin, is very broad. Here, we combined genetic, evolutionary, antigenic, and structural information to determine the most relevant regions of the hemagglutinin of human influenza A/H3N2 viruses for interaction with human immunoglobulins. We estimated the antigenic weights of amino acid changes at individual sites from hemagglutination inhibition data using antigenic tree inference followed by spatial clustering of antigenicity-altering protein sites on the protein structure. This approach determined six relevant areas (patches) for antigenic variation that had a key role in the past antigenic evolution of the viruses. Previous transitions between successive predominating antigenic types of H3N2 viruses always included amino acid changes in either the first or second antigenic patch. Interestingly, there was only partial overlap between the antigenic patches and the patches under strong positive selection. Therefore, besides alterations of antigenicity, other interactions with the host may shape the evolution of human influenza A/H3N2 viruses.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleDetermination of antigenicity-altering patches on the major surface protein of human influenza A/H3N2 viruses.en
dc.typeArticleen
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.en
dc.identifier.journalVirus evolutionen

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