A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner

Autores
Costa Navarro, Guadalupe Soledad; Pallarés, Horacio Martín; González López Ledesma, María Mora; de Borba, Luana; Mazzolenis, Romina; Gamarnik, Andrea Vanesa
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Flaviviruses are emerging and re-emerging pathogens causing widespread epidemics worldwide. Their RNA genomes play multiple roles during infection, folding into dynamic structures that regulate viral processes. To understand the mechanisms of flavivirus infection and to design genetic tools for viral countermeasures, it is important to dissect functional RNA structures present in viral genomes. Here, we investigate RNA structures within the open reading frame of the Zika virus (ZIKV) genome that regulate viral replication. We identified a functional stem-loop structure, SL1, located within the conserved C1 element in the capsid protein coding sequence of mosquito-borne flavivirus genomes. The integrity of the SL1 structure was crucial for viral RNA amplifi cation in mosquito cells and enhanced ZIKV replication in vertebrate cells. Evolution experiments in mosquito cells with lethal SL1-disrupting mutants revealed reversions and pseudo-reversions that restored SL1 structure, confirming its role as a cis-acting RNA element. We also found that a sequence within SL1 contributes to a novel genome cyclization element unique to ZIKV. This sequence folds locally into SL1 or hybridizes with a 3’ UTR sequence to extend the conserved cyclization sequence (CS1), which is known to be essential for RNA synthesis. Although the C1 element is conserved among mosquito-borne flaviviruses, the RNA structures and long-range interactions in this element required for ZIKV replication differ from those reported for dengue virus. Our studies highlight the presence of a conserved RNA element operating through distinct mechanisms in related flaviviruses. These findings offer insights into the dynamic nature of the ZIKV genome and provide information for rational flavivirus attenuation.
Fil: Costa Navarro, Guadalupe Soledad. 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: 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: González López Ledesma, María Mora. 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: 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: Mazzolenis, Romina. 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: 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
Zika virus
cis-acting viral RNAs
flavivivirus
viral genome cyclization
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/275201
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent mannerCosta Navarro, Guadalupe SoledadPallarés, Horacio MartínGonzález López Ledesma, María Morade Borba, LuanaMazzolenis, RominaGamarnik, Andrea VanesaZika viruscis-acting viral RNAsflavivivirusviral genome cyclizationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Flaviviruses are emerging and re-emerging pathogens causing widespread epidemics worldwide. Their RNA genomes play multiple roles during infection, folding into dynamic structures that regulate viral processes. To understand the mechanisms of flavivirus infection and to design genetic tools for viral countermeasures, it is important to dissect functional RNA structures present in viral genomes. Here, we investigate RNA structures within the open reading frame of the Zika virus (ZIKV) genome that regulate viral replication. We identified a functional stem-loop structure, SL1, located within the conserved C1 element in the capsid protein coding sequence of mosquito-borne flavivirus genomes. The integrity of the SL1 structure was crucial for viral RNA amplifi cation in mosquito cells and enhanced ZIKV replication in vertebrate cells. Evolution experiments in mosquito cells with lethal SL1-disrupting mutants revealed reversions and pseudo-reversions that restored SL1 structure, confirming its role as a cis-acting RNA element. We also found that a sequence within SL1 contributes to a novel genome cyclization element unique to ZIKV. This sequence folds locally into SL1 or hybridizes with a 3’ UTR sequence to extend the conserved cyclization sequence (CS1), which is known to be essential for RNA synthesis. Although the C1 element is conserved among mosquito-borne flaviviruses, the RNA structures and long-range interactions in this element required for ZIKV replication differ from those reported for dengue virus. Our studies highlight the presence of a conserved RNA element operating through distinct mechanisms in related flaviviruses. These findings offer insights into the dynamic nature of the ZIKV genome and provide information for rational flavivirus attenuation.Fil: Costa Navarro, Guadalupe Soledad. 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: 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: González López Ledesma, María Mora. 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: 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: Mazzolenis, Romina. 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: 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 Microbiology2025-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/275201Costa Navarro, Guadalupe Soledad; Pallarés, Horacio Martín; González López Ledesma, María Mora; de Borba, Luana; Mazzolenis, Romina; et al.; A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner; American Society for Microbiology; Journal of Virology; 10-2025; 1-180022-538XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/jvi.01550-25info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.01550-25info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-03T09:38:47Zoai:ri.conicet.gov.ar:11336/275201instacron: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:34982025-12-03 09:38:47.473CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
title A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
spellingShingle A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
Costa Navarro, Guadalupe Soledad
Zika virus
cis-acting viral RNAs
flavivivirus
viral genome cyclization
title_short A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
title_full A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
title_fullStr A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
title_full_unstemmed A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
title_sort A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner
dc.creator.none.fl_str_mv Costa Navarro, Guadalupe Soledad
Pallarés, Horacio Martín
González López Ledesma, María Mora
de Borba, Luana
Mazzolenis, Romina
Gamarnik, Andrea Vanesa
author Costa Navarro, Guadalupe Soledad
author_facet Costa Navarro, Guadalupe Soledad
Pallarés, Horacio Martín
González López Ledesma, María Mora
de Borba, Luana
Mazzolenis, Romina
Gamarnik, Andrea Vanesa
author_role author
author2 Pallarés, Horacio Martín
González López Ledesma, María Mora
de Borba, Luana
Mazzolenis, Romina
Gamarnik, Andrea Vanesa
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Zika virus
cis-acting viral RNAs
flavivivirus
viral genome cyclization
topic Zika virus
cis-acting viral RNAs
flavivivirus
viral genome cyclization
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 are emerging and re-emerging pathogens causing widespread epidemics worldwide. Their RNA genomes play multiple roles during infection, folding into dynamic structures that regulate viral processes. To understand the mechanisms of flavivirus infection and to design genetic tools for viral countermeasures, it is important to dissect functional RNA structures present in viral genomes. Here, we investigate RNA structures within the open reading frame of the Zika virus (ZIKV) genome that regulate viral replication. We identified a functional stem-loop structure, SL1, located within the conserved C1 element in the capsid protein coding sequence of mosquito-borne flavivirus genomes. The integrity of the SL1 structure was crucial for viral RNA amplifi cation in mosquito cells and enhanced ZIKV replication in vertebrate cells. Evolution experiments in mosquito cells with lethal SL1-disrupting mutants revealed reversions and pseudo-reversions that restored SL1 structure, confirming its role as a cis-acting RNA element. We also found that a sequence within SL1 contributes to a novel genome cyclization element unique to ZIKV. This sequence folds locally into SL1 or hybridizes with a 3’ UTR sequence to extend the conserved cyclization sequence (CS1), which is known to be essential for RNA synthesis. Although the C1 element is conserved among mosquito-borne flaviviruses, the RNA structures and long-range interactions in this element required for ZIKV replication differ from those reported for dengue virus. Our studies highlight the presence of a conserved RNA element operating through distinct mechanisms in related flaviviruses. These findings offer insights into the dynamic nature of the ZIKV genome and provide information for rational flavivirus attenuation.
Fil: Costa Navarro, Guadalupe Soledad. 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: 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: González López Ledesma, María Mora. 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: 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: Mazzolenis, Romina. 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: 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 are emerging and re-emerging pathogens causing widespread epidemics worldwide. Their RNA genomes play multiple roles during infection, folding into dynamic structures that regulate viral processes. To understand the mechanisms of flavivirus infection and to design genetic tools for viral countermeasures, it is important to dissect functional RNA structures present in viral genomes. Here, we investigate RNA structures within the open reading frame of the Zika virus (ZIKV) genome that regulate viral replication. We identified a functional stem-loop structure, SL1, located within the conserved C1 element in the capsid protein coding sequence of mosquito-borne flavivirus genomes. The integrity of the SL1 structure was crucial for viral RNA amplifi cation in mosquito cells and enhanced ZIKV replication in vertebrate cells. Evolution experiments in mosquito cells with lethal SL1-disrupting mutants revealed reversions and pseudo-reversions that restored SL1 structure, confirming its role as a cis-acting RNA element. We also found that a sequence within SL1 contributes to a novel genome cyclization element unique to ZIKV. This sequence folds locally into SL1 or hybridizes with a 3’ UTR sequence to extend the conserved cyclization sequence (CS1), which is known to be essential for RNA synthesis. Although the C1 element is conserved among mosquito-borne flaviviruses, the RNA structures and long-range interactions in this element required for ZIKV replication differ from those reported for dengue virus. Our studies highlight the presence of a conserved RNA element operating through distinct mechanisms in related flaviviruses. These findings offer insights into the dynamic nature of the ZIKV genome and provide information for rational flavivirus attenuation.
publishDate 2025
dc.date.none.fl_str_mv 2025-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/275201
Costa Navarro, Guadalupe Soledad; Pallarés, Horacio Martín; González López Ledesma, María Mora; de Borba, Luana; Mazzolenis, Romina; et al.; A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner; American Society for Microbiology; Journal of Virology; 10-2025; 1-18
0022-538X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/275201
identifier_str_mv Costa Navarro, Guadalupe Soledad; Pallarés, Horacio Martín; González López Ledesma, María Mora; de Borba, Luana; Mazzolenis, Romina; et al.; A conserved RNA structure at the capsid-coding sequence of Zika virus genome is required for viral replication in a host-dependent manner; American Society for Microbiology; Journal of Virology; 10-2025; 1-18
0022-538X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/jvi.01550-25
info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.01550-25
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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