Dengue virus capsid protein facilitates genome compaction and packaging
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/57722 |
Resumo: | © 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/). |
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Dengue virus capsid protein facilitates genome compaction and packagingRNA structureRNA-protein interactionsDengueVirus packaging© 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/).Dengue 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.The 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.MDPIRepositório da Universidade de LisboaBoon, Priscilla L. S.Silva Martins, AnaLim, Xin NiEnguita, Francisco J.Santos, Nuno C.Bond, Peter J.Wan, YueMartins, Ivo C.Huber, Roland G.2023-05-31T14:03:39Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57722engInt J Mol Sci. 2023 May 2;24(9):81581661-659610.3390/ijms240981581422-0067info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:06:31Zoai:repositorio.ul.pt:10451/57722Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:14.418398Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Dengue virus capsid protein facilitates genome compaction and packaging |
| title |
Dengue virus capsid protein facilitates genome compaction and packaging |
| spellingShingle |
Dengue virus capsid protein facilitates genome compaction and packaging Boon, Priscilla L. S. RNA structure RNA-protein interactions Dengue Virus packaging |
| title_short |
Dengue virus capsid protein facilitates genome compaction and packaging |
| title_full |
Dengue virus capsid protein facilitates genome compaction and packaging |
| title_fullStr |
Dengue virus capsid protein facilitates genome compaction and packaging |
| title_full_unstemmed |
Dengue virus capsid protein facilitates genome compaction and packaging |
| title_sort |
Dengue virus capsid protein facilitates genome compaction and packaging |
| author |
Boon, Priscilla L. S. |
| author_facet |
Boon, Priscilla L. S. Silva Martins, Ana Lim, Xin Ni Enguita, Francisco J. Santos, Nuno C. Bond, Peter J. Wan, Yue Martins, Ivo C. Huber, Roland G. |
| author_role |
author |
| author2 |
Silva Martins, Ana Lim, Xin Ni Enguita, Francisco J. Santos, Nuno C. Bond, Peter J. Wan, Yue Martins, Ivo C. Huber, Roland G. |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Boon, Priscilla L. S. Silva Martins, Ana Lim, Xin Ni Enguita, Francisco J. Santos, Nuno C. Bond, Peter J. Wan, Yue Martins, Ivo C. Huber, Roland G. |
| dc.subject.por.fl_str_mv |
RNA structure RNA-protein interactions Dengue Virus packaging |
| topic |
RNA structure RNA-protein interactions Dengue Virus packaging |
| 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/). |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-05-31T14:03:39Z 2023 2023-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/57722 |
| url |
http://hdl.handle.net/10451/57722 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Int J Mol Sci. 2023 May 2;24(9):8158 1661-6596 10.3390/ijms24098158 1422-0067 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI |
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MDPI |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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