| Author | Dias, Suelen Silva Gomes | |
| Author | Fernandes, Tamires Cunha | |
| Author | Moreira, Luciana Souza | |
| Author | Soares, Vinicius Cardoso | |
| Author | Lima, Giselle Barbosa | |
| Author | Quintanilha, Isaclaudia G. Azevedo | |
| Author | Santos, Julia | |
| Author | Dutra, Filipe Pereira | |
| Author | Freitas, Caroline | |
| Author | Reis, Patrícia A. | |
| Author | Rehen, Stevens Kastrup | |
| Author | Bozza, Fernando A. | |
| Author | Souza, Thiago M. Lopes | |
| Author | Almeida, Cecilia J. G. de | |
| Author | Bozza, Patrícia T. | |
| Access date | 2023-04-06T12:06:05Z | |
| Available date | 2023-04-06T12:06:05Z | |
| Document date | 2023 | |
| Citation | 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. | en_US |
| ISSN | 1742-2094 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57698 | |
| Language | eng | en_US |
| Publisher | BMC | en_US |
| Rights | open access | |
| Subject in Portuguese | Metabolismo lipídico | en_US |
| Subject in Portuguese | Gotículas lipídicas | en_US |
| Subject in Portuguese | Imunometabolismo | en_US |
| Subject in Portuguese | Inflamação | en_US |
| Subject in Portuguese | Zika virus | en_US |
| Subject in Portuguese | Neuroinfecção | en_US |
| Title | Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells | en_US |
| Type | Article | |
| DOI | 10.1186/s12974-023-02736-7 | |
| Abstract | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | Lipid metabolism | en_US |
| Subject | Lipid droplets | en_US |
| Subject | Immunometabolism | en_US |
| Subject | Inflammation | en_US |
| Subject | Zika virus | en_US |
| Subject | Neuroinfection | en_US |
