Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| 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/57698 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
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Dias, Suelen Silva GomesFernandes, Tamires CunhaMoreira, Luciana SouzaSoares, Vinicius CardosoLima, Giselle BarbosaQuintanilha, Isaclaudia G. AzevedoSantos, JuliaDutra, Filipe PereiraFreitas, CarolineReis, Patricia A.Rehen, Stevens KastrupBozza, Fernando A.Souza, Thiago M. LopesAlmeida, Cecilia J. G. deBozza, Patricia2023-04-06T12:06:05Z2023-04-06T12:06:05Z2023DIAS, Suelen Silva Gomes et al. Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells. Journal of Neuroinflamation, v. 20, p. 1-15, 2023.1742-2094https://www.arca.fiocruz.br/handle/icict/5769810.1186/s12974-023-02736-7engBMCMetabolismo lipídicoGotículas lipídicasImunometabolismoInflamaçãoZika virusNeuroinfecçãoLipid metabolismLipid dropletsImmunometabolismInflammationZika virusNeuroinfectionMetabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. 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. Programa de Imunologia e Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Estadual do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Rio de Janeiro, RJ, Brasil.Instituto D’Or de Pesquisa e Ensino. Rio de Janeiro. RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biologia, Rio de Janeiro, RJ, Brasil.Instituto D’Or de Pesquisa e Ensino. Rio de Janeiro. RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas, Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.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/57698/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALPatriciaBozza_Suelen_DIas_etal_IOC_2023.pdfPatriciaBozza_Suelen_DIas_etal_IOC_2023.pdfapplication/pdf1993618https://www.arca.fiocruz.br/bitstream/icict/57698/2/PatriciaBozza_Suelen_DIas_etal_IOC_2023.pdf68834a5cee3e0453e412e463a655aa91MD52icict/576982023-09-14 15:46:54.488oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-14T18:46:54Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| title |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| spellingShingle |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells Dias, Suelen Silva Gomes Metabolismo lipídico Gotículas lipídicas Imunometabolismo Inflamação Zika virus Neuroinfecção Lipid metabolism Lipid droplets Immunometabolism Inflammation Zika virus Neuroinfection |
| title_short |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| title_full |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| title_fullStr |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| title_full_unstemmed |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| title_sort |
Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells |
| author |
Dias, Suelen Silva Gomes |
| author_facet |
Dias, Suelen Silva Gomes Fernandes, Tamires Cunha Moreira, Luciana Souza Soares, Vinicius Cardoso Lima, Giselle Barbosa Quintanilha, Isaclaudia G. Azevedo Santos, Julia Dutra, Filipe Pereira Freitas, Caroline Reis, Patricia A. Rehen, Stevens Kastrup Bozza, Fernando A. Souza, Thiago M. Lopes Almeida, Cecilia J. G. de Bozza, Patricia |
| author_role |
author |
| author2 |
Fernandes, Tamires Cunha Moreira, Luciana Souza Soares, Vinicius Cardoso Lima, Giselle Barbosa Quintanilha, Isaclaudia G. Azevedo Santos, Julia Dutra, Filipe Pereira Freitas, Caroline Reis, Patricia A. Rehen, Stevens Kastrup Bozza, Fernando A. Souza, Thiago M. Lopes Almeida, Cecilia J. G. de Bozza, Patricia |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Dias, Suelen Silva Gomes Fernandes, Tamires Cunha Moreira, Luciana Souza Soares, Vinicius Cardoso Lima, Giselle Barbosa Quintanilha, Isaclaudia G. Azevedo Santos, Julia Dutra, Filipe Pereira Freitas, Caroline Reis, Patricia A. Rehen, Stevens Kastrup Bozza, Fernando A. Souza, Thiago M. Lopes Almeida, Cecilia J. G. de Bozza, Patricia |
| dc.subject.other.en_US.fl_str_mv |
Metabolismo lipídico Gotículas lipídicas Imunometabolismo Inflamação Zika virus Neuroinfecção |
| topic |
Metabolismo lipídico Gotículas lipídicas Imunometabolismo Inflamação Zika virus Neuroinfecção Lipid metabolism Lipid droplets Immunometabolism Inflammation Zika virus Neuroinfection |
| dc.subject.en.en_US.fl_str_mv |
Lipid metabolism Lipid droplets Immunometabolism Inflammation Zika virus Neuroinfection |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
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2023 |
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2023-04-06T12:06:05Z |
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2023-04-06T12:06:05Z |
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2023 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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DIAS, Suelen Silva Gomes et al. Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells. Journal of Neuroinflamation, v. 20, p. 1-15, 2023. |
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https://www.arca.fiocruz.br/handle/icict/57698 |
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1742-2094 |
| dc.identifier.doi.none.fl_str_mv |
10.1186/s12974-023-02736-7 |
| identifier_str_mv |
DIAS, Suelen Silva Gomes et al. Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells. Journal of Neuroinflamation, v. 20, p. 1-15, 2023. 1742-2094 10.1186/s12974-023-02736-7 |
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