Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

dc.creatorCumberworth, Stephanie L.
dc.creatorBarrie, Jennifer A.
dc.creatorCunningham, Madeleine E.
dc.creatorFigueiredo, Daniely Paulino Gomes de
dc.creatorSchultz, Verena
dc.creatorWilder-Smith, Adrian J.
dc.creatorBrennan, Benjamin
dc.creatorPena, Lindomar J.
dc.creatorFrança, Rafael Freitas de Oliveira
dc.creatorLinington, Christopher
dc.creatorBarnett, Susan C.
dc.creatorWillison, Hugh J.
dc.creatorKohl, Alain
dc.creatorEdgar, Julia M.
dc.date2018-01-17T12:44:37Z
dc.date2018-01-17T12:44:37Z
dc.date2017
dc.date.accessioned2023-09-27T00:12:25Z
dc.date.available2023-09-27T00:12:25Z
dc.identifierCUMBERWORTH, S. L. et al. Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected. Acta Neuropathologica Communications, v. 5, n. 1, p. 1-16, Dec. 2017.
dc.identifier2051-5960
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/23933
dc.identifier10.1186/s40478-017-0450-8
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898521
dc.descriptionVídeo Relacionado ao artigo: https://www.youtube.com/watch?v=Tpc3rW9zsb8
dc.descriptionEste estudo foi financiado pelo UK Medical Research Council [MC_UU_12014, MR / N017552 / 1 (AK); Resposta rápida ZIKA MC_PC_15105 (HW, JME, AK); MR / K501335 / 1 (Bolsa de Treinamento de Doutorado, SLC)], Centro Nacional de Reposição, Redução e Refinamento (NC / L000423 / 1, JME, CL) e Wellcome Trust (203680 / Z / 16 / Z, WT092805; HJW). Este projecto foi parcialmente financiado através do programa de investigação e inovação Horizonte 2020 da União Europeia no âmbito do acordo de subvenção ZikaPLAN n.º 734584 (HJW, JME, SB, CL).
dc.descriptionThe recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences.
dc.formatapplication/pdf
dc.languageeng
dc.rightsopen access
dc.subjectAxon
dc.subjectSistema nervoso central
dc.subjectMurine
dc.subjectMielina
dc.subjectSistema nervoso periférico
dc.subjectTropismo
dc.subjectVírus Zika
dc.subjectAxon
dc.subjectCentral nervous system
dc.subjectMurine
dc.subjectMyelin
dc.subjectPeripheral nervous system
dc.subjectTropism
dc.subjectZika virus
dc.subjectZika virus
dc.subjectSistema Nervoso
dc.titleZika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected
dc.typeArticle


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