Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/32914 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil. |
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Silva, Emiliana M.Conde, Jonas N.Allonso, DiegoVentura, Gustavo T.Coelho, Diego R.Carneiro, Pedro HenriqueSilva, Manuela L.Paes, Marciano V.Rabelo, KíssilaWeissmuller, GilbertoBisch, Paulo MascarelloMohana-Borges, Ronaldo2019-05-02T15:49:17Z2019-05-02T15:49:17Z2019SILVA, Emiliana M. et al. Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity. Scientific Reports, v. 9, n. 2651, 19p, 2019.2045-2322https://www.arca.fiocruz.br/handle/icict/3291410.1038/s41598-019-39157-7engNature ResearchVírus da DengueProteina NS3DENV2proteína GAPDHMecanismo molecularAlterações hepáticasDengue virusDENV2 NS3 proteinGAPDH proteinMolecular mechanismHepatic alterationsDengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Biotecnologia Farmacêutica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biodiversidade e Sustentabilidade. Macaé, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisa Médica. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Laboratório de Ultraestrutura e Biologia Tecidual. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Física Biológica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Física Biológica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Dengue is an important mosquito-borne disease and a global public health problem. The disease is caused by dengue virus (DENV), which is a member of the Flaviviridae family and contains a positive single-stranded RNA genome that encodes a single precursor polyprotein that is further cleaved into structural and non-structural proteins. Among these proteins, the non-structural 3 (NS3) protein is very important because it forms a non-covalent complex with the NS2B cofactor, thereby forming the functional viral protease. NS3 also contains a C-terminal ATPase/helicase domain that is essential for RNA replication. Here, we identified 47 NS3-interacting partners using the yeast two-hybrid system. Among those partners, we highlight several proteins involved in host energy metabolism, such as apolipoprotein H, aldolase B, cytochrome C oxidase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH directly binds full-length NS3 and its isolated helicase and protease domains. Moreover, we observed an intense colocalization between the GAPDH and NS3 proteins in DENV2-infected Huh7.5.1 cells, in NS3-transfected BHK-21 cells and in hepatic tissue from a fatal dengue case. Taken together, these results suggest that the human GAPDH-DENV NS3 interaction is involved in hepatic metabolic alterations, which may contribute to the appearance of steatosis in dengue-infected patients. The interaction between GAPDH and full-length NS3 or its helicase domain in vitro as well as in NS3-transfected cells resulted in decreased GAPDH glycolytic activity. Reduced GAPDH glycolytic activity may lead to the accumulation of metabolic intermediates, shifting metabolism to alternative, non-glycolytic pathways. This report is the first to identify the interaction of the DENV2 NS3 protein with the GAPDH protein and to demonstrate that this interaction may play an important role in the molecular mechanism that triggers hepatic alterations.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/32914/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMarciano_Paes_etal_IOC_2019.pdfMarciano_Paes_etal_IOC_2019.pdfapplication/pdf2757474https://www.arca.fiocruz.br/bitstream/icict/32914/2/Marciano_Paes_etal_IOC_2019.pdff484f68c0e57cb9176253927e0d15291MD52TEXTMarciano_Paes_etal_IOC_2019.pdf.txtMarciano_Paes_etal_IOC_2019.pdf.txtExtracted texttext/plain88853https://www.arca.fiocruz.br/bitstream/icict/32914/3/Marciano_Paes_etal_IOC_2019.pdf.txtda52980897820af932bec097c2737754MD53icict/329142019-05-03 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dc.title.pt_BR.fl_str_mv |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
title |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
spellingShingle |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity Silva, Emiliana M. Vírus da Dengue Proteina NS3 DENV2 proteína GAPDH Mecanismo molecular Alterações hepáticas Dengue virus DENV2 NS3 protein GAPDH protein Molecular mechanism Hepatic alterations |
title_short |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
title_full |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
title_fullStr |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
title_full_unstemmed |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
title_sort |
Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity |
author |
Silva, Emiliana M. |
author_facet |
Silva, Emiliana M. Conde, Jonas N. Allonso, Diego Ventura, Gustavo T. Coelho, Diego R. Carneiro, Pedro Henrique Silva, Manuela L. Paes, Marciano V. Rabelo, Kíssila Weissmuller, Gilberto Bisch, Paulo Mascarello Mohana-Borges, Ronaldo |
author_role |
author |
author2 |
Conde, Jonas N. Allonso, Diego Ventura, Gustavo T. Coelho, Diego R. Carneiro, Pedro Henrique Silva, Manuela L. Paes, Marciano V. Rabelo, Kíssila Weissmuller, Gilberto Bisch, Paulo Mascarello Mohana-Borges, Ronaldo |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Silva, Emiliana M. Conde, Jonas N. Allonso, Diego Ventura, Gustavo T. Coelho, Diego R. Carneiro, Pedro Henrique Silva, Manuela L. Paes, Marciano V. Rabelo, Kíssila Weissmuller, Gilberto Bisch, Paulo Mascarello Mohana-Borges, Ronaldo |
dc.subject.other.pt_BR.fl_str_mv |
Vírus da Dengue Proteina NS3 DENV2 proteína GAPDH Mecanismo molecular Alterações hepáticas |
topic |
Vírus da Dengue Proteina NS3 DENV2 proteína GAPDH Mecanismo molecular Alterações hepáticas Dengue virus DENV2 NS3 protein GAPDH protein Molecular mechanism Hepatic alterations |
dc.subject.en.pt_BR.fl_str_mv |
Dengue virus DENV2 NS3 protein GAPDH protein Molecular mechanism Hepatic alterations |
description |
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-05-02T15:49:17Z |
dc.date.available.fl_str_mv |
2019-05-02T15:49:17Z |
dc.date.issued.fl_str_mv |
2019 |
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 |
SILVA, Emiliana M. et al. Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity. Scientific Reports, v. 9, n. 2651, 19p, 2019. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/32914 |
dc.identifier.issn.pt_BR.fl_str_mv |
2045-2322 |
dc.identifier.doi.none.fl_str_mv |
10.1038/s41598-019-39157-7 |
identifier_str_mv |
SILVA, Emiliana M. et al. Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity. Scientific Reports, v. 9, n. 2651, 19p, 2019. 2045-2322 10.1038/s41598-019-39157-7 |
url |
https://www.arca.fiocruz.br/handle/icict/32914 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Nature Research |
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Nature Research |
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