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2017-06-23Zeitschriftenartikel DOI: 10.18452/20975
Stochastic Model of Acidification, Activation of Hemagglutinin and Escape of Influenza Viruses from an Endosome
dc.contributor.authorLagache, Thibault
dc.contributor.authorSieben, Christian
dc.contributor.authorMeyer, Tim
dc.contributor.authorHerrmann, Andreas
dc.contributor.authorholcman, david
dc.date.accessioned2019-12-19T11:42:33Z
dc.date.available2019-12-19T11:42:33Z
dc.date.issued2017-06-23none
dc.date.updated2019-10-15T08:11:29Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/21726
dc.description.abstractInfluenza viruses enter the cell inside an endosome. During the endosomal journey, acidification triggers a conformational change of the virus spike protein hemagglutinin (HA) that results in escape of the viral genome from the endosome into the cytoplasm. It is still unclear how the interplay between acidification and HA conformation changes affects the kinetics of the viral endosomal escape. We develop here a stochastic model to estimate the change of conformation of HAs inside the endosome nanodomain. Using a Markov process, we model the arrival of protons to HA binding sites and compute the kinetics of their accumulation. We compute the Mean First Passage Time (MFPT) of the number of HA bound sites to a threshold, which is used to estimate the HA activation rate for a given pH (i.e. proton concentration). The present analysis reveals that HA proton binding sites possess a high chemical barrier, ensuring a stability of the spike protein at sub-acidic pH. We predict that activating more than 3 adjacent HAs is necessary to trigger endosomal fusion and this configuration prevents premature release of viruses from early endosomes.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectmodelingeng
dc.subjectfirst passage timeeng
dc.subjectasymptotic analysiseng
dc.subjectconformational changeeng
dc.subjectendosomal acidificationeng
dc.subjectinfluenza viruseng
dc.subjecttraffickingeng
dc.subjectKramers-Moyal approximationeng
dc.subject.ddc530 Physiknone
dc.titleStochastic Model of Acidification, Activation of Hemagglutinin and Escape of Influenza Viruses from an Endosomenone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/21726-1
dc.identifier.doihttp://dx.doi.org/10.18452/20975
dc.type.versionpublishedVersionnone
local.edoc.pages15none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn2296-424X
dcterms.bibliographicCitation.doi10.3389/fphy.2017.00025none
dcterms.bibliographicCitation.journaltitleFrontiers in Physicsnone
dcterms.bibliographicCitation.volume5none
dcterms.bibliographicCitation.articlenumber25none
dcterms.bibliographicCitation.originalpublishernameFrontiers Media S.A.none
dcterms.bibliographicCitation.originalpublisherplaceLausannenone
bua.departmentLebenswissenschaftliche Fakultätnone

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