dc.contributor.author | Ruokolainen, Visa | |
dc.contributor.author | Domanska, Aušra | |
dc.contributor.author | Laajala, Mira | |
dc.contributor.author | Pelliccia, Maria | |
dc.contributor.author | Butcher, Sarah J. | |
dc.contributor.author | Marjomäki, Varpu | |
dc.date.accessioned | 2019-08-22T06:57:17Z | |
dc.date.available | 2020-02-13T22:35:27Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Ruokolainen, 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. <i>Journal of Virology</i>, <i>93</i>(17), Article e00599-19. <a href="https://doi.org/10.1128/JVI.00599-19" target="_blank">https://doi.org/10.1128/JVI.00599-19</a> | |
dc.identifier.other | CONVID_31229163 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/65266 | |
dc.description.abstract | ABSTRACT 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.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.publisher | American Society for Microbiology | |
dc.relation.ispartofseries | Journal of Virology | |
dc.rights | In Copyright | |
dc.subject.other | cryoEM structure | |
dc.subject.other | albumin | |
dc.subject.other | enterovirus | |
dc.subject.other | uncoating | |
dc.title | Extracellular albumin and endosomal ions prime enterovirus particles for uncoating that can be prevented by fatty acid saturation | |
dc.type | research article | |
dc.identifier.urn | URN:NBN:fi:jyu-201908213867 | |
dc.contributor.laitos | Bio- ja ympäristötieteiden laitos | fi |
dc.contributor.laitos | Department of Biological and Environmental Science | en |
dc.contributor.oppiaine | Solu- ja molekyylibiologia | fi |
dc.contributor.oppiaine | Cell and Molecular Biology | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.date.updated | 2019-08-21T15:15:16Z | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.relation.issn | 0022-538X | |
dc.relation.numberinseries | 17 | |
dc.relation.volume | 93 | |
dc.type.version | acceptedVersion | |
dc.rights.copyright | © 2019 American Society for Microbiology | |
dc.rights.accesslevel | openAccess | fi |
dc.type.publication | article | |
dc.relation.grantnumber | | |
dc.subject.yso | virologia | |
dc.subject.yso | enterovirukset | |
dc.subject.yso | albumiinit | |
dc.subject.yso | rasvahapot | |
dc.subject.yso | biokemia | |
dc.subject.yso | ionit | |
dc.format.content | fulltext | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p14570 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p20689 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p20319 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p4800 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p1375 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p9015 | |
dc.rights.url | http://rightsstatements.org/page/InC/1.0/?language=en | |
dc.relation.doi | 10.1128/JVI.00599-19 | |
dc.relation.funder | Jane ja Aatos Erkon säätiö | fi |
dc.relation.funder | Jane and Aatos Erkko Foundation | en |
jyx.fundingprogram | Säätiö | fi |
jyx.fundingprogram | Foundation | en |
jyx.fundinginformation | This work was supported by the Academy of Finland (275199 and 315950 to S.J.B.; 257125 to V.M.), the Sigrid Juselius Foundation (S.J.B.), and Jane and Aatos Erkko foundation (V.M.). | |
dc.type.okm | A1 | |