Dengue virus capsid protein usurps lipid droplets for viral particle formation

Autores
Samsa, Marcelo Mario Alejandro; Mondotte, Juan Alberto; Iglesias, Nestor Gabriel; Assunção Miranda, Iranaia; Barbosa Lima, Giselle; Da Poian, Andrea T.; Bozza, Patricia T.; Gamarnik, Andrea Vanesa
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the mechanisms of dengue virus genome amplification. However, little is known about the process by which the capsid protein recruits the viral genome during encapsidation. Here, we found that the mature capsid protein in the cytoplasm of dengue virus infected cells accumulates on the surface of ER-derived organelles named lipid droplets. Mutagenesis analysis using infectious dengue virus clones has identified specific hydrophobic amino acids, located in the center of the capsid protein, as key elements for lipid droplet association. Substitutions of amino acid L50 or L54 in the capsid protein disrupted lipid droplet targeting and impaired viral particle formation. We also report that dengue virus infection increases the number of lipid droplets per cell, suggesting a link between lipid droplet metabolism and viral replication. In this regard, we found that pharmacological manipulation of the amount of lipid droplets in the cell can be a means to control dengue virus replication. In addition, we developed a novel genetic system to dissociate cis-acting RNA replication elements from the capsid coding sequence. Using this system, we found that mislocalization of a mutated capsid protein decreased viral RNA amplification. We propose that lipid droplets play multiple roles during the viral life cycle; they could sequester the viral capsid protein early during infection and provide a scaffold for genome encapsidation.
Fil: Samsa, Marcelo Mario Alejandro. 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: Mondotte, Juan Alberto. 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: Iglesias, Nestor Gabriel. 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: Assunção Miranda, Iranaia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barbosa Lima, Giselle. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: Da Poian, Andrea T.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bozza, Patricia T.. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
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
Lipid droplets
Dengue virus
Encapsidation
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:11336/25925
Acceder
id CONICETDig_b8765f07932470a55d7b87b0d535f11a
oai_identifier_str oai:ri.conicet.gov.ar:11336/25925
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dengue virus capsid protein usurps lipid droplets for viral particle formationSamsa, Marcelo Mario AlejandroMondotte, Juan AlbertoIglesias, Nestor GabrielAssunção Miranda, IranaiaBarbosa Lima, GiselleDa Poian, Andrea T.Bozza, Patricia T.Gamarnik, Andrea VanesaLipid dropletsDengue virusEncapsidationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the mechanisms of dengue virus genome amplification. However, little is known about the process by which the capsid protein recruits the viral genome during encapsidation. Here, we found that the mature capsid protein in the cytoplasm of dengue virus infected cells accumulates on the surface of ER-derived organelles named lipid droplets. Mutagenesis analysis using infectious dengue virus clones has identified specific hydrophobic amino acids, located in the center of the capsid protein, as key elements for lipid droplet association. Substitutions of amino acid L50 or L54 in the capsid protein disrupted lipid droplet targeting and impaired viral particle formation. We also report that dengue virus infection increases the number of lipid droplets per cell, suggesting a link between lipid droplet metabolism and viral replication. In this regard, we found that pharmacological manipulation of the amount of lipid droplets in the cell can be a means to control dengue virus replication. In addition, we developed a novel genetic system to dissociate cis-acting RNA replication elements from the capsid coding sequence. Using this system, we found that mislocalization of a mutated capsid protein decreased viral RNA amplification. We propose that lipid droplets play multiple roles during the viral life cycle; they could sequester the viral capsid protein early during infection and provide a scaffold for genome encapsidation.Fil: Samsa, Marcelo Mario Alejandro. 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: Mondotte, Juan Alberto. 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: Iglesias, Nestor Gabriel. 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: Assunção Miranda, Iranaia. Universidade Federal do Rio de Janeiro; BrasilFil: Barbosa Lima, Giselle. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; BrasilFil: Da Poian, Andrea T.. Universidade Federal do Rio de Janeiro; BrasilFil: Bozza, Patricia T.. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; BrasilFil: 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; ArgentinaPublic Library of Science2009-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25925Samsa, Marcelo Mario Alejandro; Mondotte, Juan Alberto; Iglesias, Nestor Gabriel; Assunção Miranda, Iranaia; Barbosa Lima, Giselle; et al.; Dengue virus capsid protein usurps lipid droplets for viral particle formation; Public Library of Science; Plos Pathogens; 5; 10; 10-2009; 1-141553-73661553-7374CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000632info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1000632info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:53Zoai:ri.conicet.gov.ar:11336/25925instacron: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 09:43:53.804CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dengue virus capsid protein usurps lipid droplets for viral particle formation
title Dengue virus capsid protein usurps lipid droplets for viral particle formation
spellingShingle Dengue virus capsid protein usurps lipid droplets for viral particle formation
Samsa, Marcelo Mario Alejandro
Lipid droplets
Dengue virus
Encapsidation
title_short Dengue virus capsid protein usurps lipid droplets for viral particle formation
title_full Dengue virus capsid protein usurps lipid droplets for viral particle formation
title_fullStr Dengue virus capsid protein usurps lipid droplets for viral particle formation
title_full_unstemmed Dengue virus capsid protein usurps lipid droplets for viral particle formation
title_sort Dengue virus capsid protein usurps lipid droplets for viral particle formation
dc.creator.none.fl_str_mv Samsa, Marcelo Mario Alejandro
Mondotte, Juan Alberto
Iglesias, Nestor Gabriel
Assunção Miranda, Iranaia
Barbosa Lima, Giselle
Da Poian, Andrea T.
Bozza, Patricia T.
Gamarnik, Andrea Vanesa
author Samsa, Marcelo Mario Alejandro
author_facet Samsa, Marcelo Mario Alejandro
Mondotte, Juan Alberto
Iglesias, Nestor Gabriel
Assunção Miranda, Iranaia
Barbosa Lima, Giselle
Da Poian, Andrea T.
Bozza, Patricia T.
Gamarnik, Andrea Vanesa
author_role author
author2 Mondotte, Juan Alberto
Iglesias, Nestor Gabriel
Assunção Miranda, Iranaia
Barbosa Lima, Giselle
Da Poian, Andrea T.
Bozza, Patricia T.
Gamarnik, Andrea Vanesa
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lipid droplets
Dengue virus
Encapsidation
topic Lipid droplets
Dengue virus
Encapsidation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the mechanisms of dengue virus genome amplification. However, little is known about the process by which the capsid protein recruits the viral genome during encapsidation. Here, we found that the mature capsid protein in the cytoplasm of dengue virus infected cells accumulates on the surface of ER-derived organelles named lipid droplets. Mutagenesis analysis using infectious dengue virus clones has identified specific hydrophobic amino acids, located in the center of the capsid protein, as key elements for lipid droplet association. Substitutions of amino acid L50 or L54 in the capsid protein disrupted lipid droplet targeting and impaired viral particle formation. We also report that dengue virus infection increases the number of lipid droplets per cell, suggesting a link between lipid droplet metabolism and viral replication. In this regard, we found that pharmacological manipulation of the amount of lipid droplets in the cell can be a means to control dengue virus replication. In addition, we developed a novel genetic system to dissociate cis-acting RNA replication elements from the capsid coding sequence. Using this system, we found that mislocalization of a mutated capsid protein decreased viral RNA amplification. We propose that lipid droplets play multiple roles during the viral life cycle; they could sequester the viral capsid protein early during infection and provide a scaffold for genome encapsidation.
Fil: Samsa, Marcelo Mario Alejandro. 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: Mondotte, Juan Alberto. 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: Iglesias, Nestor Gabriel. 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: Assunção Miranda, Iranaia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barbosa Lima, Giselle. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: Da Poian, Andrea T.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Bozza, Patricia T.. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
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 Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the mechanisms of dengue virus genome amplification. However, little is known about the process by which the capsid protein recruits the viral genome during encapsidation. Here, we found that the mature capsid protein in the cytoplasm of dengue virus infected cells accumulates on the surface of ER-derived organelles named lipid droplets. Mutagenesis analysis using infectious dengue virus clones has identified specific hydrophobic amino acids, located in the center of the capsid protein, as key elements for lipid droplet association. Substitutions of amino acid L50 or L54 in the capsid protein disrupted lipid droplet targeting and impaired viral particle formation. We also report that dengue virus infection increases the number of lipid droplets per cell, suggesting a link between lipid droplet metabolism and viral replication. In this regard, we found that pharmacological manipulation of the amount of lipid droplets in the cell can be a means to control dengue virus replication. In addition, we developed a novel genetic system to dissociate cis-acting RNA replication elements from the capsid coding sequence. Using this system, we found that mislocalization of a mutated capsid protein decreased viral RNA amplification. We propose that lipid droplets play multiple roles during the viral life cycle; they could sequester the viral capsid protein early during infection and provide a scaffold for genome encapsidation.
publishDate 2009
dc.date.none.fl_str_mv 2009-10
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/11336/25925
Samsa, Marcelo Mario Alejandro; Mondotte, Juan Alberto; Iglesias, Nestor Gabriel; Assunção Miranda, Iranaia; Barbosa Lima, Giselle; et al.; Dengue virus capsid protein usurps lipid droplets for viral particle formation; Public Library of Science; Plos Pathogens; 5; 10; 10-2009; 1-14
1553-7366
1553-7374
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25925
identifier_str_mv Samsa, Marcelo Mario Alejandro; Mondotte, Juan Alberto; Iglesias, Nestor Gabriel; Assunção Miranda, Iranaia; Barbosa Lima, Giselle; et al.; Dengue virus capsid protein usurps lipid droplets for viral particle formation; Public Library of Science; Plos Pathogens; 5; 10; 10-2009; 1-14
1553-7366
1553-7374
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000632
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1000632
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
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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score 13.13397

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