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Dengue virus capsid protein facilitates genome compaction and packaging

2023Artigo científico Acesso aberto
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dc.contributor.authorBoon, Priscilla L. S.
dc.contributor.authorSilva Martins, Ana
dc.contributor.authorLim, Xin Ni
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorSantos, Nuno C.
dc.contributor.authorBond, Peter J.
dc.contributor.authorWan, Yue
dc.contributor.authorMartins, Ivo C.
dc.contributor.authorHuber, Roland G.
dc.date.accessioned2023-05-31T14:03:39Z
dc.date.available2023-05-31T14:03:39Z
dc.date.issued2023
dc.description© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractDengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigated the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrated that C protein interaction with DENV genomes saturates at an RNA:C protein ratio below 1:250. Moreover, we also showed that the length of the RNA genome interaction sites varies, in a multimodal distribution, consistent with the C protein binding to each RNA site mostly in singlets or pairs (and, in some instances, higher numbers). We showed that interaction sites are preferentially sites with low base pairing, as previously measured by 2'-acetylation analyzed by primer extension (SHAPE) reactivity indicating structuredness. We found a clear association pattern emerged: RNA-C protein binding sites are strongly associated with long-range RNA-RNA interaction sites, particularly inside virions. This, in turn, explains the need for C protein in viral genome packaging: the protein has a chief role in coordinating these key interactions, promoting proper packaging of viral RNA. Such sites are, thus, highly consequential for viral assembly, and, as such, may be targeted in future drug development strategies against these and related viruses.pt_PT
dc.description.sponsorshipThe computational work for this article was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg). This research is supported by A*STAR 202D800013 to R.G.H. P.J.B. is supported by BII (A*STAR). This research was also supported by Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), Project PTDC/SAU-ENB/117013/2010 and Exploratory Project 2022.02763.PTDC, as well as by the Calouste Gulbenkian Foundation (FCG, Portugal), project Science Frontiers Research Prize 2010. I.C.M. acknowledges consecutive funding from FCT-MCTES programs “Investigador FCT” (research contract IF/00772/2013) and “Stimulus of Scientific Employment” (research contract CEECIND/01670/2017). A.S.M. acknowledges FCT-MCTES fellowship PD/BD/113698/2015 and partial support from an European Molecular Biology Organization (EMBO) short-term fellowship.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2023 May 2;24(9):8158pt_PT
dc.identifier.doi10.3390/ijms24098158pt_PT
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10451/57722
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationA nanotechnology approach to Flavivirus-targeted drug development strategies
dc.relationNot Available
dc.relationA nanotechnology approach to Flavivirus-targeted drug development strategies
dc.relation.publisherversionhttps://www.mdpi.com/journal/ijmspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectRNA structurept_PT
dc.subjectRNA-protein interactionspt_PT
dc.subjectDenguept_PT
dc.subjectVirus packagingpt_PT
dc.titleDengue virus capsid protein facilitates genome compaction and packagingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleA nanotechnology approach to Flavivirus-targeted drug development strategies
oaire.awardTitleNot Available
oaire.awardTitleA nanotechnology approach to Flavivirus-targeted drug development strategies
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-ENB%2F117013%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/2022.02763.PTDC/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00772%2F2013%2FCP1170%2FCT0004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F01670%2F2017%2FCP1396%2FCT0005/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F113698%2F2015/PT
oaire.citation.issue9pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume24pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamInvestigador FCT
oaire.fundingStreamCEEC IND 2017
person.familyNameSilva Martins
person.familyNameEnguita
person.familyNameSantos
person.familyNameMartins
person.givenNameAna
person.givenNameFrancisco J.
person.givenNameNuno
person.givenNameIvo
person.identifier173306
person.identifier.ciencia-idB215-8D49-3218
person.identifier.ciencia-idCD13-5E3A-A3C5
person.identifier.ciencia-id8C17-BB8B-E8DB
person.identifier.orcid0000-0002-9586-1772
person.identifier.orcid0000-0002-8072-8557
person.identifier.orcid0000-0002-0580-0475
person.identifier.orcid0000-0002-9284-8599
person.identifier.ridA-2347-2009
person.identifier.ridN-7248-2013
person.identifier.ridG-2534-2013
person.identifier.scopus-author-id57195420299
person.identifier.scopus-author-id6602119231
person.identifier.scopus-author-id55940818300
person.identifier.scopus-author-id8628164300
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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