Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells

dc.creatorDias, Suelen Silva Gomes
dc.creatorFernandes, Tamires Cunha
dc.creatorMoreira, Luciana Souza
dc.creatorSoares, Vinicius Cardoso
dc.creatorLima, Giselle Barbosa
dc.creatorQuintanilha, Isaclaudia G. Azevedo
dc.creatorSantos, Julia
dc.creatorDutra, Filipe Pereira
dc.creatorFreitas, Caroline
dc.creatorReis, Patricia A.
dc.creatorRehen, Stevens Kastrup
dc.creatorBozza, Fernando A.
dc.creatorSouza, Thiago M. Lopes
dc.creatorAlmeida, Cecilia J. G. de
dc.creatorBozza, Patricia
dc.date2023-04-06T12:06:05Z
dc.date2023-04-06T12:06:05Z
dc.date2023
dc.date.accessioned2023-09-26T20:16:06Z
dc.date.available2023-09-26T20:16:06Z
dc.identifierDIAS, 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.
dc.identifier1742-2094
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/57698
dc.identifier10.1186/s12974-023-02736-7
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8852899
dc.descriptionZika 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBMC
dc.rightsopen access
dc.subjectMetabolismo lipídico
dc.subjectGotículas lipídicas
dc.subjectImunometabolismo
dc.subjectInflamação
dc.subjectZika virus
dc.subjectNeuroinfecção
dc.subjectLipid metabolism
dc.subjectLipid droplets
dc.subjectImmunometabolism
dc.subjectInflammation
dc.subjectZika virus
dc.subjectNeuroinfection
dc.titleMetabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells
dc.typeArticle


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