Dengue virus capsid protein usurps lipid droplets for viral particle formation

Bibliographic Details
Main Author: Samsa, Marcelo M.
Publication Date: 2009
Other Authors: Mondotte, Juan A., Iglesias, Nestor G., Miranda, Iranaia Assunção, Lima, Giselle Barbosa, da Poian, Andrea T., Bozza, Patrícia T., Gamarnik, Andrea V.
Format: Article
Language: eng
Source: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.1371/journal.ppat.1000632
Download full: https://arca.fiocruz.br/handle/icict/30957
Summary: Fundación Instituto Leloir-CONICET. Buenos Aires, Argentina.
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spelling Samsa, Marcelo M.Mondotte, Juan A.Iglesias, Nestor G.Miranda, Iranaia AssunçãoLima, Giselle Barbosada Poian, Andrea T.Bozza, Patrícia T.Gamarnik, Andrea V.2019-01-10T13:24:40Z2019-01-10T13:24:40Z2009SAMSA, Marcelo M. et al. Dengue Virus Capsid Protein Usurps Lipid Droplets for Viral Particle Formation. PLoS Pathog., v. 5, n. 10, p. 1-14, Oct. 2009.1553-7366https://arca.fiocruz.br/handle/icict/3095710.1371/journal.ppat.10006321553-7374engBioMed CentralVírus da DengueProteína de capsídeoGotículas lipídicasFormação de Partículas ViraisDengue virusLipid DropletsCapsid ProteinViral Particle FormationDengue virus capsid protein usurps lipid droplets for viral particle formationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundación Instituto Leloir-CONICET. Buenos Aires, Argentina.Fundación Instituto Leloir-CONICET. Buenos Aires, Argentina.Fundación Instituto Leloir-CONICET. Buenos Aires, Argentina.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundación Instituto Leloir-CONICET. Buenos Aires, Argentina.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/81732812-8adb-4a99-afc7-0b6358f9cd00/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALpatriciabozza_etal_IOC_2009.pdfpatriciabozza_etal_IOC_2009.pdfapplication/pdf1137555https://arca.fiocruz.br/bitstreams/39ff5d59-9a3d-4a16-ac8a-c80810386e24/downloadbe0f476c60443ed1d388867a757583f9MD52trueAnonymousREADTEXTpatriciabozza_etal_IOC_2009.pdf.txtpatriciabozza_etal_IOC_2009.pdf.txtExtracted texttext/plain79343https://arca.fiocruz.br/bitstreams/fe7c1ec6-ff0f-41aa-92e2-b1d8d1913ac2/downloada3e01c7cc6cbf333a6c76222ad28d216MD55falseAnonymousREADTHUMBNAILpatriciabozza_etal_IOC_2009.pdf.jpgpatriciabozza_etal_IOC_2009.pdf.jpgGenerated Thumbnailimage/jpeg6624https://arca.fiocruz.br/bitstreams/f0fef23d-3647-4357-ba29-4309b9d60d56/download502c3713a0381466581f43c1460e5716MD56falseAnonymousREADicict/309572025-07-29 23:44:34.251open.accessoai:arca.fiocruz.br:icict/30957https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-07-30T02:44:34Repositório Institucional da FIOCRUZ (ARCA) - 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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 M.
Vírus da Dengue
Proteína de capsídeo
Gotículas lipídicas
Formação de Partículas Virais
Dengue virus
Lipid Droplets
Capsid Protein
Viral Particle Formation
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
author Samsa, Marcelo M.
author_facet Samsa, Marcelo M.
Mondotte, Juan A.
Iglesias, Nestor G.
Miranda, Iranaia Assunção
Lima, Giselle Barbosa
da Poian, Andrea T.
Bozza, Patrícia T.
Gamarnik, Andrea V.
author_role author
author2 Mondotte, Juan A.
Iglesias, Nestor G.
Miranda, Iranaia Assunção
Lima, Giselle Barbosa
da Poian, Andrea T.
Bozza, Patrícia T.
Gamarnik, Andrea V.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Samsa, Marcelo M.
Mondotte, Juan A.
Iglesias, Nestor G.
Miranda, Iranaia Assunção
Lima, Giselle Barbosa
da Poian, Andrea T.
Bozza, Patrícia T.
Gamarnik, Andrea V.
dc.subject.other.none.fl_str_mv Vírus da Dengue
Proteína de capsídeo
Gotículas lipídicas
Formação de Partículas Virais
topic Vírus da Dengue
Proteína de capsídeo
Gotículas lipídicas
Formação de Partículas Virais
Dengue virus
Lipid Droplets
Capsid Protein
Viral Particle Formation
dc.subject.en.none.fl_str_mv Dengue virus
Lipid Droplets
Capsid Protein
Viral Particle Formation
description Fundación Instituto Leloir-CONICET. Buenos Aires, Argentina.
publishDate 2009
dc.date.issued.fl_str_mv 2009
dc.date.accessioned.fl_str_mv 2019-01-10T13:24:40Z
dc.date.available.fl_str_mv 2019-01-10T13:24:40Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SAMSA, Marcelo M. et al. Dengue Virus Capsid Protein Usurps Lipid Droplets for Viral Particle Formation. PLoS Pathog., v. 5, n. 10, p. 1-14, Oct. 2009.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/30957
dc.identifier.issn.none.fl_str_mv 1553-7366
dc.identifier.doi.none.fl_str_mv 10.1371/journal.ppat.1000632
dc.identifier.eissn.none.fl_str_mv 1553-7374
identifier_str_mv SAMSA, Marcelo M. et al. Dengue Virus Capsid Protein Usurps Lipid Droplets for Viral Particle Formation. PLoS Pathog., v. 5, n. 10, p. 1-14, Oct. 2009.
1553-7366
10.1371/journal.ppat.1000632
1553-7374
url https://arca.fiocruz.br/handle/icict/30957
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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