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dc.contributor.authorRuokolainen, Visa
dc.contributor.authorDomanska, Aušra
dc.contributor.authorLaajala, Mira
dc.contributor.authorPelliccia, Maria
dc.contributor.authorButcher, Sarah J.
dc.contributor.authorMarjomäki, Varpu
dc.date.accessioned2019-08-22T06:57:17Z
dc.date.available2020-02-13T22:35:27Z
dc.date.issued2019fi
dc.identifier.citationRuokolainen, V., Domanska, A., Laajala, M., Pelliccia, M., Butcher, S. J., & Marjomäki, V. (2019). Extracellular albumin and endosomal ions prime enterovirus particles for uncoating that can be prevented by fatty acid saturation. <em>Journal of Virology</em>, 93 (17), e00599-19. <a href="https://doi.org/10.1128/JVI.00599-19">doi:10.1128/JVI.00599-19</a>fi
dc.identifier.otherTUTKAID_81747
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/65266
dc.description.abstractABSTRACT There is limited information about the molecular triggers leading to the uncoating of enteroviruses under physiological conditions. Using real-time spectroscopy and sucrose gradients with radioactively labeled virus, we show at 37°C, the formation of albumin-triggered, metastable uncoating intermediate of echovirus 1 without receptor engagement. This conversion was blocked by saturating the albumin with fatty acids. High potassium but low sodium and calcium concentrations, mimicking the endosomal environment, also induced the formation of a metastable uncoating intermediate of echovirus 1. Together, these factors boosted the formation of the uncoating intermediate, and the infectivity of this intermediate was retained, as judged by end-point titration. Cryo-electron microscopy reconstruction of the virions treated with albumin and high potassium, low sodium, and low calcium concentrations resulted in a 3.6-Å resolution model revealing a fenestrated capsid showing 4% expansion and loss of the pocket factor, similarly to altered (A) particles described for other enteroviruses. The dimer interface between VP2 molecules was opened, the VP1 N termini disordered and most likely externalized. The RNA was clearly visible, anchored to the capsid. The results presented here suggest that extracellular albumin, partially saturated with fatty acids, likely leads to the formation of the infectious uncoating intermediate prior to the engagement with the cellular receptor. In addition, changes in mono- and divalent cations, likely occurring in endosomes, promote capsid opening and genome release. IMPORTANCE There is limited information about the uncoating of enteroviruses under physiological conditions. Here, we focused on physiologically relevant factors that likely contribute to opening of echovirus 1 and other B-group enteroviruses. By combining biochemical and structural data, we show that, before entering cells, extracellular albumin is capable of priming the virus into a metastable yet infectious intermediate state. The ionic changes that are suggested to occur in endosomes can further contribute to uncoating and promote genome release, once the viral particle is endocytosed. Importantly, we provide a detailed high-resolution structure of a virion after treatment with albumin and a preset ion composition, showing pocket factor release, capsid expansion, and fenestration and the clearly visible genome still anchored to the capsid. This study provides valuable information about the physiological factors that contribute to the opening of B group enteroviruses.fi
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofseriesJournal of Virology
dc.rightsIn Copyright
dc.subject.othervirologiafi
dc.subject.otherenteroviruksetfi
dc.subject.otheralbumiinitfi
dc.subject.otherrasvahapotfi
dc.subject.othercryoEM structurefi
dc.subject.otheralbuminfi
dc.subject.otherbiochemistryfi
dc.subject.otherenterovirusfi
dc.subject.otherfatty acidsfi
dc.subject.otherionsfi
dc.subject.otheruncoatingfi
dc.subject.othervirologyfi
dc.titleExtracellular albumin and endosomal ions prime enterovirus particles for uncoating that can be prevented by fatty acid saturationfi
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201908213867
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosThe Department of Biological and Environmental Scienceen
dc.contributor.oppiaineSolu- ja molekyylibiologia
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2019-08-21T15:15:16Z
dc.description.reviewstatuspeerReviewed
dc.relation.issn0022-538X
dc.relation.numberinseries17
dc.relation.volume93
dc.type.versionacceptedVersion
dc.rights.copyright© 2019 American Society for Microbiology
dc.rights.accesslevelopenAccessfi
dc.format.contentfulltext
dc.rights.urlhttp://rightsstatements.org/page/InC/1.0/?language=en
dc.relation.doi10.1128/JVI.00599-19


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