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dc.contributor.authorCastaño Rodríguez, Carlos
dc.contributor.authorHonrubia, José M.
dc.contributor.authorGutiérrez-Álvarez, Javier
dc.contributor.authorDe Diego, Marta L.
dc.contributor.authorNieto Torres, José L.
dc.contributor.authorJiménez Guardeño, José M.
dc.contributor.authorRegla Nava, José A.
dc.contributor.authorFernández Delgado, Raúl
dc.contributor.authorVerdiá Báguena, Carmen
dc.contributor.authorQueralt-Martín, María
dc.contributor.authorKochan, Grazyna
dc.contributor.authorPerlman, Stanley
dc.contributor.authorAguilella, Vicente
dc.contributor.authorSola, Isabel
dc.contributor.authorEnjuanes, Luis
dc.date.accessioned2019-01-29T12:01:53Z
dc.date.available2019-01-29T12:01:53Z
dc.date.issued2018
dc.identifier.citationCastaño-Rodriguez C, Honrubia JM, Gutiérrez-Álvarez J, DeDiego ML, Nieto-Torres JL, Jimenez-Guardeño JM, Regla-Nava JA, Fernandez-Delgado R, Verdia-Báguena C, Queralt-Martín M, Kochan G, Perlman S, Aguilella VM, Sola I, Enjuanes L. 2018. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. mBio 9:e02325-17. https://doi .org/10.1128/mBio.02325-17.ca_CA
dc.identifier.issn2150-7511
dc.identifier.urihttp://hdl.handle.net/10234/180359
dc.description.abstractViroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice. IMPORTANCE Collectively, these results demonstrate key roles for the ion channel and PBM domains in optimal virus replication and pathogenesis and suggest that the viral viroporins and PBMs are suitable targets for antiviral therapy and for mutation in attenuated SARS-CoV vaccines.ca_CA
dc.format.extent23 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherAmerican Society for Microbiologyca_CA
dc.relation.isPartOfmBio May/June 2018 Volume 9 Issue 3 e02325-17ca_CA
dc.rightst © 2018 Castaño-Rodriguez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.ca_CA
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/4.0/*
dc.subjectcoronavirusca_CA
dc.subjectPBMca_CA
dc.subjectPDZca_CA
dc.subjectSARS-CoVca_CA
dc.subjectviroporinsca_CA
dc.titleRole of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesisca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttps://doi.org/10.1128/mBio.02325-17
dc.relation.projectID(BIO2013-42869-R and BIO2016-75549-R AEI/FEDER, UE ; IMI_JU_115760 ; 0258-3413/HHSN266200700010C ; 2P01AI060699 ; R01 AI129269 ; FIS2013-40473-P and FIS2016-75257-P AEI/FEDER, UE ; (P1.1B2015-28ca_CA
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttps://mbio.asm.org/content/9/3/e02325-17ca_CA
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_CA


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t © 2018 Castaño-Rodriguez et al.
This is an open-access article distributed under
the terms of the Creative Commons Attribution
4.0 International license.
Excepto si se señala otra cosa, la licencia del ítem se describe como: t © 2018 Castaño-Rodriguez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.