RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity?
- Autores
- de Borba, Luana; Villordo, Sergio; Marsico, Franco Leonel; Carballeda, Juan Manuel; Filomatori, Claudia Veronica; Gebhard, Leopoldo German; Pallarés, Horacio Martín; Lequime, Sebastian; Lambrechts, Louis; Sánchez Vargas, Irma; Blair, Carol D.; Gamarnik, Andrea Vanesa
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Flaviviruses include a diverse group of medically important viruses that cycle between mosquitoes and humans. During this natural process of switching hosts, each species imposes different selective forces on the viral population. Using dengue virus (DENV) as model, we found that paralogous RNA structures originating from duplications in the viral 3′ untranslated region (UTR) are under different selective pressures in the two hosts. These RNA structures, known as dumbbells (DB1 and DB2), were originally proposed to be enhancers of viral replication. Analysis of viruses obtained from infected mosquitoes showed selection of mutations that mapped in DB2. Recombinant viruses carrying the identified variations confirmed that these mutations greatly increase viral replication in mosquito cells, with low or no impact in human cells. Use of viruses lacking each of the DB structures revealed opposite viral phenotypes. While deletion of DB1 reduced viral replication about 10-fold, viruses lacking DB2 displayed a great increase of fitness in mosquitoes, confirming a functional diversification of these similar RNA elements. Mechanistic analysis indicated that DB1 and DB2 differentially modulate viral genome cyclization and RNA replication. We found that a pseudoknot formed within DB2 competes with long-range RNA-RNA interactions that are necessary for minus-strand RNA synthesis. Our results support a model in which a functional diversification of duplicated RNA elements in the viral 3′ UTR is driven by host-specific requirements. This study provides new ideas for understanding molecular aspects of the evolution of RNA viruses that naturally jump between different species.
Fil: de Borba, Luana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Marsico, Franco Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Carballeda, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Gebhard, Leopoldo German. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Pallarés, Horacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Lequime, Sebastian. Institut Pasteur de Paris.; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Lambrechts, Louis. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Fil: Sánchez Vargas, Irma. State University of Colorado - Fort Collins; Estados Unidos
Fil: Blair, Carol D.. State University of Colorado - Fort Collins; Estados Unidos
Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina - Materia
-
DENV
ZIKV
RNA STRUCTURE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/105027
Ver los metadatos del registro completo
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RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity?de Borba, LuanaVillordo, SergioMarsico, Franco LeonelCarballeda, Juan ManuelFilomatori, Claudia VeronicaGebhard, Leopoldo GermanPallarés, Horacio MartínLequime, SebastianLambrechts, LouisSánchez Vargas, IrmaBlair, Carol D.Gamarnik, Andrea VanesaDENVZIKVRNA STRUCTUREhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Flaviviruses include a diverse group of medically important viruses that cycle between mosquitoes and humans. During this natural process of switching hosts, each species imposes different selective forces on the viral population. Using dengue virus (DENV) as model, we found that paralogous RNA structures originating from duplications in the viral 3′ untranslated region (UTR) are under different selective pressures in the two hosts. These RNA structures, known as dumbbells (DB1 and DB2), were originally proposed to be enhancers of viral replication. Analysis of viruses obtained from infected mosquitoes showed selection of mutations that mapped in DB2. Recombinant viruses carrying the identified variations confirmed that these mutations greatly increase viral replication in mosquito cells, with low or no impact in human cells. Use of viruses lacking each of the DB structures revealed opposite viral phenotypes. While deletion of DB1 reduced viral replication about 10-fold, viruses lacking DB2 displayed a great increase of fitness in mosquitoes, confirming a functional diversification of these similar RNA elements. Mechanistic analysis indicated that DB1 and DB2 differentially modulate viral genome cyclization and RNA replication. We found that a pseudoknot formed within DB2 competes with long-range RNA-RNA interactions that are necessary for minus-strand RNA synthesis. Our results support a model in which a functional diversification of duplicated RNA elements in the viral 3′ UTR is driven by host-specific requirements. This study provides new ideas for understanding molecular aspects of the evolution of RNA viruses that naturally jump between different species.Fil: de Borba, Luana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Marsico, Franco Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Carballeda, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gebhard, Leopoldo German. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Pallarés, Horacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lequime, Sebastian. Institut Pasteur de Paris.; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lambrechts, Louis. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; FranciaFil: Sánchez Vargas, Irma. State University of Colorado - Fort Collins; Estados UnidosFil: Blair, Carol D.. State University of Colorado - Fort Collins; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaAmerican Society for Microbiology2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105027de Borba, Luana; Villordo, Sergio; Marsico, Franco Leonel; Carballeda, Juan Manuel; Filomatori, Claudia Veronica; et al.; RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity?; American Society for Microbiology; mBio; 10; 1; 1-2019; 1-18; e025062150-7511CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://mbio.asm.org/content/10/1/e02506-18.longinfo:eu-repo/semantics/altIdentifier/doi/10.1128/mBio.02506-18info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:06Zoai:ri.conicet.gov.ar:11336/105027instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:06.606CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| title |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| spellingShingle |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? de Borba, Luana DENV ZIKV RNA STRUCTURE |
| title_short |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| title_full |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| title_fullStr |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| title_full_unstemmed |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| title_sort |
RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity? |
| dc.creator.none.fl_str_mv |
de Borba, Luana Villordo, Sergio Marsico, Franco Leonel Carballeda, Juan Manuel Filomatori, Claudia Veronica Gebhard, Leopoldo German Pallarés, Horacio Martín Lequime, Sebastian Lambrechts, Louis Sánchez Vargas, Irma Blair, Carol D. Gamarnik, Andrea Vanesa |
| author |
de Borba, Luana |
| author_facet |
de Borba, Luana Villordo, Sergio Marsico, Franco Leonel Carballeda, Juan Manuel Filomatori, Claudia Veronica Gebhard, Leopoldo German Pallarés, Horacio Martín Lequime, Sebastian Lambrechts, Louis Sánchez Vargas, Irma Blair, Carol D. Gamarnik, Andrea Vanesa |
| author_role |
author |
| author2 |
Villordo, Sergio Marsico, Franco Leonel Carballeda, Juan Manuel Filomatori, Claudia Veronica Gebhard, Leopoldo German Pallarés, Horacio Martín Lequime, Sebastian Lambrechts, Louis Sánchez Vargas, Irma Blair, Carol D. Gamarnik, Andrea Vanesa |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
DENV ZIKV RNA STRUCTURE |
| topic |
DENV ZIKV RNA STRUCTURE |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
Flaviviruses include a diverse group of medically important viruses that cycle between mosquitoes and humans. During this natural process of switching hosts, each species imposes different selective forces on the viral population. Using dengue virus (DENV) as model, we found that paralogous RNA structures originating from duplications in the viral 3′ untranslated region (UTR) are under different selective pressures in the two hosts. These RNA structures, known as dumbbells (DB1 and DB2), were originally proposed to be enhancers of viral replication. Analysis of viruses obtained from infected mosquitoes showed selection of mutations that mapped in DB2. Recombinant viruses carrying the identified variations confirmed that these mutations greatly increase viral replication in mosquito cells, with low or no impact in human cells. Use of viruses lacking each of the DB structures revealed opposite viral phenotypes. While deletion of DB1 reduced viral replication about 10-fold, viruses lacking DB2 displayed a great increase of fitness in mosquitoes, confirming a functional diversification of these similar RNA elements. Mechanistic analysis indicated that DB1 and DB2 differentially modulate viral genome cyclization and RNA replication. We found that a pseudoknot formed within DB2 competes with long-range RNA-RNA interactions that are necessary for minus-strand RNA synthesis. Our results support a model in which a functional diversification of duplicated RNA elements in the viral 3′ UTR is driven by host-specific requirements. This study provides new ideas for understanding molecular aspects of the evolution of RNA viruses that naturally jump between different species. Fil: de Borba, Luana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Marsico, Franco Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Carballeda, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Gebhard, Leopoldo German. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes; Argentina Fil: Pallarés, Horacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Lequime, Sebastian. Institut Pasteur de Paris.; Francia. Centre National de la Recherche Scientifique; Francia Fil: Lambrechts, Louis. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia Fil: Sánchez Vargas, Irma. State University of Colorado - Fort Collins; Estados Unidos Fil: Blair, Carol D.. State University of Colorado - Fort Collins; Estados Unidos Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina |
| description |
Flaviviruses include a diverse group of medically important viruses that cycle between mosquitoes and humans. During this natural process of switching hosts, each species imposes different selective forces on the viral population. Using dengue virus (DENV) as model, we found that paralogous RNA structures originating from duplications in the viral 3′ untranslated region (UTR) are under different selective pressures in the two hosts. These RNA structures, known as dumbbells (DB1 and DB2), were originally proposed to be enhancers of viral replication. Analysis of viruses obtained from infected mosquitoes showed selection of mutations that mapped in DB2. Recombinant viruses carrying the identified variations confirmed that these mutations greatly increase viral replication in mosquito cells, with low or no impact in human cells. Use of viruses lacking each of the DB structures revealed opposite viral phenotypes. While deletion of DB1 reduced viral replication about 10-fold, viruses lacking DB2 displayed a great increase of fitness in mosquitoes, confirming a functional diversification of these similar RNA elements. Mechanistic analysis indicated that DB1 and DB2 differentially modulate viral genome cyclization and RNA replication. We found that a pseudoknot formed within DB2 competes with long-range RNA-RNA interactions that are necessary for minus-strand RNA synthesis. Our results support a model in which a functional diversification of duplicated RNA elements in the viral 3′ UTR is driven by host-specific requirements. This study provides new ideas for understanding molecular aspects of the evolution of RNA viruses that naturally jump between different species. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-01 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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http://hdl.handle.net/11336/105027 de Borba, Luana; Villordo, Sergio; Marsico, Franco Leonel; Carballeda, Juan Manuel; Filomatori, Claudia Veronica; et al.; RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity?; American Society for Microbiology; mBio; 10; 1; 1-2019; 1-18; e02506 2150-7511 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/105027 |
| identifier_str_mv |
de Borba, Luana; Villordo, Sergio; Marsico, Franco Leonel; Carballeda, Juan Manuel; Filomatori, Claudia Veronica; et al.; RNA Structure Duplication in the Dengue Virus 3′ UTR: Redundancy or Host Specificity?; American Society for Microbiology; mBio; 10; 1; 1-2019; 1-18; e02506 2150-7511 CONICET Digital CONICET |
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eng |
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eng |
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American Society for Microbiology |
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American Society for Microbiology |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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