Zur Kurzanzeige

2015-06-19Zeitschriftenartikel DOI: 10.1038/srep11434
In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
dc.contributor.authorSchmier, Sonja
dc.contributor.authorMostafa, Ahmed
dc.contributor.authorHaarmann, Thomas
dc.contributor.authorBannert, Norbert
dc.contributor.authorZiebuhr, John
dc.contributor.authorVeljkovic, Veljko
dc.contributor.authorDietrich, Ursula
dc.contributor.authorPleschka, Stephan
dc.date.accessioned2018-05-07T18:20:32Z
dc.date.available2018-05-07T18:20:32Z
dc.date.created2015-08-04
dc.date.issued2015-06-19none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reygdMVZzLgQ/PDF/24V1NXO8QKA2c.pdf
dc.identifier.urihttp://edoc.rki.de/176904/2093
dc.description.abstractNewly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Biologische Sicherheit
dc.subjectAnimalseng
dc.subjectHumanseng
dc.subjectGenetic Vectors/geneticseng
dc.subjectPhenotypeeng
dc.subjectMutationeng
dc.subjectCell Lineeng
dc.subjectGene Expressioneng
dc.subjectModels Moleculareng
dc.subjectComputer Simulationeng
dc.subjectVirus Replicationeng
dc.subjectModels Biologicaleng
dc.subjectAmino Acidseng
dc.subjectHemagglutinin Glycoproteins Influenza Virus/chemistryeng
dc.subjectHemagglutinin Glycoproteins Influenza Virus/geneticseng
dc.subjectInfluenza A Virus H5N1 Subtype/geneticseng
dc.subjectInfluenza A Virus H5N1 Subtype/metabolismeng
dc.subjectProtein Conformationeng
dc.subjectReceptors Virus/geneticseng
dc.subjectReceptors Virus/metabolismeng
dc.subjectRetroviridae/geneticseng
dc.subjectVirus Attachmenteng
dc.subject.ddc610 Medizin
dc.titleIn Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10040008
dc.identifier.doi10.1038/srep11434
dc.identifier.doihttp://dx.doi.org/10.25646/2018
local.edoc.container-titleScientific Reports
local.edoc.container-textSchmier, S., Mostafa, A., Haarmann, T., Bannert, N., Ziebuhr, J., Veljkovic, V., Dietrich, U., Pleschka, S. In silico prediction and experimental confirmation of HA residues conferring enhanced human receptor specificity of H5N1 influenza A viruses (2015) Scientific Reports, 5, art. no. 11434.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.nature.com/srep/2015/150619/srep11434/full/srep11434.html
local.edoc.container-publisher-nameNature Publishing Group
local.edoc.container-issue11434
local.edoc.container-year2015

Zur Kurzanzeige