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Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination\u2014which is critical for saltatory conduction and neuronal function\u2014has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/v13010091","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T20:32:47Z","timestamp":1610397167000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8172-1525","authenticated-orcid":false,"given":"Verena","family":"Schultz","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Cumberworth","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Gu","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-6082","authenticated-orcid":false,"given":"Natasha","family":"Johnson","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-0707","authenticated-orcid":false,"given":"Claire L.","family":"Donald","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"McCanney","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Barrie","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Da Silva Filipe","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Linington","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J.","family":"Willison","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Edgar","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan C.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Kohl","sequence":"additional","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, 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Pathogenicity and physical properties","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus I. Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1128\/CMR.00072-15","article-title":"Zika Virus","volume":"29","author":"Musso","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1602113","article-title":"Zika Virus","volume":"374","author":"Petersen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41579-018-0134-9","article-title":"The evolution of Zika virus from Asia to the Americas","volume":"17","author":"Liu","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/S0140-6736(17)31450-2","article-title":"An update on Zika virus infection","volume":"390","author":"Baud","year":"2017","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41559-019-0836-z","article-title":"Vector-borne transmission and evolution of Zika virus","volume":"3","author":"Piedra","year":"2019","journal-title":"Nat. Ecol. Evol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.micinf.2018.01.006","article-title":"An overview of mosquito vectors of Zika virus","volume":"20","author":"Boyer","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1021\/acs.chemrev.7b00719","article-title":"Biochemistry and Molecular Biology of Flaviviruses","volume":"118","author":"Barrows","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.virusres.2017.08.015","article-title":"Functional RNA during Zika virus infection","volume":"254","author":"Goertz","year":"2018","journal-title":"Virus Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Haddow, A.D., Schuh, A.J., Yasuda, C.Y., Kasper, M.R., Heang, V., Huy, R., Guzman, H., Tesh, R.B., and Weaver, S.C. (2012). Genetic characterization of Zika virus strains: Geographic expansion of the Asian lineage. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001477"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJMra1808246","article-title":"Zika Virus Infection\u2014After the Pandemic","volume":"381","author":"Musso","year":"2019","journal-title":"New Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12250-018-0078-2","article-title":"The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas","volume":"34","author":"Hu","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/S1473-3099(19)30293-2","article-title":"Emergence of the Asian lineage of Zika virus in Angola: An outbreak investigation","volume":"19","author":"Hill","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.cell.2019.07.018","article-title":"Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic","volume":"178","author":"Grubaugh","year":"2019","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1093\/brain\/aww158","article-title":"Zika virus-associated neurological disorders: A review","volume":"139","author":"Araujo","year":"2016","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shang, P., Zhu, M., Wang, Y., Zheng, X., Wu, X., Zhu, J., Feng, J., and Zhang, H.L. (2020). Axonal variants of Guillain-Barre syndrome: An update. J. Neurol.","DOI":"10.1007\/s00415-020-09742-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1128\/JVI.00252-16","article-title":"Zika Virus: New Clinical Syndromes and Its Emergence in the Western Hemisphere","volume":"90","author":"Lazear","year":"2016","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Pardy, R.D., and Richer, M.J. (2019). Zika Virus Pathogenesis: From Early Case Reports to Epidemics. Viruses, 11.","DOI":"10.3390\/v11100886"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41586-018-0446-y","article-title":"The emergence of Zika virus and its new clinical syndromes","volume":"560","author":"Pierson","year":"2018","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Klase, Z.A., Khakhina, S., Schneider Ade, B., Callahan, M.V., Glasspool-Malone, J., and Malone, R. (2016). Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. PLoS Negl. Trop. Dis., 10.","DOI":"10.1101\/050674"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S1473-3099(17)30727-2","article-title":"Association between microcephaly, Zika virus infection, and other risk factors in Brazil: Final report of a case-control study","volume":"18","author":"Ximenes","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"598","DOI":"10.2105\/AJPH.2016.303115","article-title":"Initial Description of the Presumed Congenital Zika Syndrome","volume":"106","author":"Martelli","year":"2016","journal-title":"Am. J. Public Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"689","DOI":"10.7326\/M16-0332","article-title":"Emergence of Congenital Zika Syndrome: Viewpoint From the Front Lines","volume":"164","author":"Costa","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e12744","DOI":"10.1111\/cmi.12744","article-title":"Zika infection and the development of neurological defects","volume":"19","author":"Russo","year":"2017","journal-title":"Cell Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.chom.2017.01.004","article-title":"Zika Virus Pathogenesis and Tissue Tropism","volume":"21","author":"Miner","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00031.2018","article-title":"Myelin in the Central Nervous System: Structure, Function, and Pathology","volume":"99","author":"Stadelmann","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134916","DOI":"10.1016\/j.neulet.2020.134916","article-title":"Neuron-oligodendroglia interactions: Activity-dependent regulation of cellular signaling","volume":"727","author":"Thornton","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.devcel.2015.01.016","article-title":"Dynamics and mechanisms of CNS myelination","volume":"32","author":"Bercury","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature11007","article-title":"Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity","volume":"485","author":"Funfschilling","year":"2012","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fnins.2018.00467","article-title":"The Axon-Myelin Unit in Development and Degenerative Disease","volume":"12","author":"Stassart","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nm.4193","article-title":"Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate","volume":"22","author":"Kapur","year":"2016","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gurung, S., Reuter, N., Preno, A., Dubaut, J., Nadeau, H., Hyatt, K., Singleton, K., Martin, A., Parks, W.T., and Papin, J.F. (2019). Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007507"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s12035-018-1263-x","article-title":"Zika Virus and the Metabolism of Neuronal Cells","volume":"56","author":"Rothan","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1093\/cid\/ciw613","article-title":"Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases","volume":"63","author":"Braga","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","first-page":"i1901","article-title":"Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: Retrospective case series study","volume":"353","author":"Coeli","year":"2016","journal-title":"BMJ"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s00401-017-1699-5","article-title":"The spectrum of neuropathological changes associated with congenital Zika virus infection","volume":"133","author":"Chimelli","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1242\/dev.143768","article-title":"Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage","volume":"143","author":"Shao","year":"2016","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ebiom.2017.10.019","article-title":"American Strain of Zika Virus Causes More Severe Microcephaly Than an Old Asian Strain in Neonatal Mice","volume":"25","author":"Zhang","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41421-018-0042-1","article-title":"Disruption of glial cell development by Zika virus contributes to severe microcephalic newborn mice","volume":"4","author":"Li","year":"2018","journal-title":"Cell Discov."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaar2749","DOI":"10.1126\/scitranslmed.aar2749","article-title":"Acute and chronic neurological consequences of early-life Zika virus infection in mice","volume":"10","author":"Frost","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroimage.2017.12.097","article-title":"The development of brain white matter microstructure","volume":"182","author":"Lebel","year":"2018","journal-title":"Neuroimage"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nbd.2015.07.007","article-title":"Cellular and molecular introduction to brain development","volume":"92","author":"Jiang","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40478-017-0450-8","article-title":"Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected","volume":"5","author":"Cumberworth","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S897","DOI":"10.1093\/infdis\/jix511","article-title":"Neuroviruses Emerging in the Americas Study. Neurological Implications of Zika Virus Infection in Adults","volume":"216","author":"Munoz","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(16)00644-9","article-title":"Acute myelitis due to Zika virus infection","volume":"387","author":"Mecharles","year":"2016","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/jamaneurol.2017.1703","article-title":"Neurologic Complications Associated With the Zika Virus in Brazilian Adults","volume":"74","author":"Frontera","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.4269\/ajtmh.17-0106","article-title":"Guillain-Barre Syndrome, Acute Disseminated Encephalomyelitis and Encephalitis Associated with Zika Virus Infection in Brazil: Detection of Viral RNA and Isolation of Virus during Late Infection","volume":"97","author":"Moreira","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000453396","article-title":"Acute Disseminated Encephalomyelitis Following Zika Virus Infection","volume":"77","author":"Niemeyer","year":"2017","journal-title":"Eur. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"ofw203","DOI":"10.1093\/ofid\/ofw203","article-title":"Zika Virus Causing Encephalomyelitis Associated With Immunoactivation","volume":"3","author":"Galliez","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1177\/1352458518781992","article-title":"Zika virus found in brain tissue of a multiple sclerosis patient undergoing an acute disseminated encephalomyelitis-like episode","volume":"25","author":"Lima","year":"2019","journal-title":"Mult. Scler."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jcv.2016.08.297","article-title":"Fatal encephalitis associated with Zika virus infection in an adult","volume":"83","author":"Soares","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMc1602964","article-title":"Zika Virus Associated with Meningoencephalitis","volume":"374","author":"Carteaux","year":"2016","journal-title":"New Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4269\/ajtmh.16-0921","article-title":"Case Report: Zika Virus Meningoencephalitis and Myelitis and Associated Magnetic Resonance Imaging Findings","volume":"97","author":"Pradhan","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.mayocp.2016.12.019","article-title":"Zika Virus Meningoencephalitis in an Immunocompromised Patient","volume":"92","author":"Schwartzmann","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1002\/acn3.575","article-title":"Impact of Zika Virus on adult human brain structure and functional organization","volume":"5","author":"Wirsich","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1038\/s41467-019-11866-7","article-title":"Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice","volume":"10","author":"Figueiredo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1002\/jnr.21084","article-title":"Murine spinal cord explants: A model for evaluating axonal growth and myelination in vitro","volume":"84","author":"Thomson","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1111\/j.1460-9568.2008.06415.x","article-title":"Myelinated, synapsing cultures of murine spinal cord--validation as an in vitro model of the central nervous system","volume":"28","author":"Thomson","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/glia.20650","article-title":"Astrocytes, but not olfactory ensheathing cells or Schwann cells, promote myelination of CNS axons in vitro","volume":"56","author":"Sorensen","year":"2008","journal-title":"Glia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/glia.22278","article-title":"The development of a rat in vitro model of spinal cord injury demonstrating the additive effects of Rho and ROCK inhibitors on neurite outgrowth and myelination","volume":"60","author":"Boomkamp","year":"2012","journal-title":"Glia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1111\/bph.12588","article-title":"Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model","volume":"171","author":"Boomkamp","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/dbio.1996.0090","article-title":"Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell","volume":"175","author":"Reynolds","year":"1996","journal-title":"Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Donald, C.L., Brennan, B., Cumberworth, S.L., Rezelj, V.V., Clark, J.J., Cordeiro, M.T., Freitas de Oliveira Franca, R., Pena, L.J., Wilkie, G.S., and Da Silva Filipe, A. (2016). Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005048"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1210\/me.2008-0169","article-title":"Axl and Tyro3 modulate female reproduction by influencing gonadotropin-releasing hormone neuron survival and migration","volume":"22","author":"Pierce","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1097\/TP.0b013e3181b47f25","article-title":"Galectin-9 significantly prolongs the survival of fully mismatched cardiac allografts in mice","volume":"88","author":"He","year":"2009","journal-title":"Transplantation"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eaax2421","DOI":"10.1126\/scitranslmed.aax2421","article-title":"Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site","volume":"12","author":"Bryden","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00234-17","DOI":"10.1128\/mSphere.00234-17","article-title":"Differential Antagonism of Human Innate Immune Responses by Tick-Borne Phlebovirus Nonstructural Proteins","volume":"2","author":"Rezelj","year":"2017","journal-title":"mSphere"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1111\/j.1471-4159.1991.tb06367.x","article-title":"Monoclonal antibodies against myelin proteolipid protein: Identification and characterization of two major determinants","volume":"57","author":"Yamamura","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: Image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S935","DOI":"10.1093\/infdis\/jix515","article-title":"Zika Virus Structure, Maturation, and Receptors","volume":"216","author":"Sirohi","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00418-013-1108-7","article-title":"Topographic regulation of neuronal intermediate filaments by phosphorylation, role of peptidyl-prolyl isomerase 1: Significance in neurodegeneration","volume":"140","author":"Binukumar","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.cytogfr.2014.05.002","article-title":"IFIT1: A dual sensor and effector molecule that detects non-2\u2019-O methylated viral RNA and inhibits its translation","volume":"25","author":"Diamond","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"W147","DOI":"10.1093\/nar\/gkw419","article-title":"Heatmapper: Web-enabled heat mapping for all","volume":"44","author":"Babicki","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12974-019-1443-2","article-title":"The role of microglia in viral encephalitis: A review","volume":"16","author":"Chen","year":"2019","journal-title":"J. NeuroInflamm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12974-016-0748-7","article-title":"Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects","volume":"13","author":"Lindqvist","year":"2016","journal-title":"J. NeuroInflamm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/glia.23562","article-title":"Low sulfated heparins target multiple proteins for central nervous system repair","volume":"67","author":"McCanney","year":"2019","journal-title":"Glia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"13028","DOI":"10.1523\/JNEUROSCI.1449-11.2011","article-title":"Functional duality of astrocytes in myelination","volume":"31","author":"Nash","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nm.2324","article-title":"A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis","volume":"17","author":"Nikic","year":"2011","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/ana.96","article-title":"Electrically active axons degenerate when exposed to nitric oxide","volume":"49","author":"Smith","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Cai, H., Chen, H., Yi, T., Daimon, C.M., Boyle, J.P., Peers, C., Maudsley, S., and Martin, B. (2013). VennPlex--a novel Venn diagram program for comparing and visualizing datasets with differentially regulated datapoints. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053388"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/ana.24748","article-title":"Zika virus: An emergent neuropathological agent","volume":"80","author":"White","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1136\/jnnp-2016-314310","article-title":"Zika virus infection and Guillain-Barre syndrome: A review focused on clinical and electrophysiological subtypes","volume":"88","author":"Uncini","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1038\/s41598-018-28257-5","article-title":"Zika Virus Replication in Dorsal Root Ganglia Explants from Interferon Receptor1 Knockout Mice Causes Myelin Degeneration","volume":"8","author":"Volpi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ircmb.2018.08.004","article-title":"Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System","volume":"344","author":"Kawasaki","year":"2019","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/glia.22375","article-title":"Oligodendroglia are limited in type I interferon induction and responsiveness in vivo","volume":"60","author":"Kapil","year":"2012","journal-title":"Glia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.brainres.2015.09.021","article-title":"The immunomodulatory oligodendrocyte","volume":"1641","author":"Zeis","year":"2016","journal-title":"Brain Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fncel.2014.00264","article-title":"Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis","volume":"8","author":"Michlmayr","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Salinas, S., Constant, O., Desmetz, C., Barthelemy, J., Lemaitre, J.M., Milhavet, O., Nagot, N., Foulongne, V., Perrin, F.E., and Saiz, J.C. (2017). Deleterious effect of Usutu virus on human neural cells. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005913"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Cle, M., Barthelemy, J., Desmetz, C., Foulongne, V., Lapeyre, L., Bollore, K., Tuaillon, E., Erkilic, N., Kalatzis, V., and Lecollinet, S. (2020). Study of Usutu virus neuropathogenicity in mice and human cellular models. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008223"},{"key":"ref_95","first-page":"1003","article-title":"Neuroinflammation Induces Neurodegeneration","volume":"1","author":"Kempuraj","year":"2016","journal-title":"J. Neurol. Neurosurg. Spine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"849","DOI":"10.17219\/acem\/68846","article-title":"CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroinflammation and neurodegeneration","volume":"27","author":"Koper","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1128\/JVI.74.3.1415-1424.2000","article-title":"A central role for CD4(+) T cells and RANTES in virus-induced central nervous system inflammation and demyelination","volume":"74","author":"Lane","year":"2000","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jneuroim.2007.05.015","article-title":"High production of RANTES and MIP-1alpha in the tropical spastic paraparesis\/HTLV-1-associated myelopathy (TSP\/HAM)","volume":"188","author":"Montanheiro","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.4049\/jimmunol.167.7.4091","article-title":"Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis","volume":"167","author":"Liu","year":"2001","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1093\/brain\/awv102","article-title":"Fibroblast growth factor signalling in multiple sclerosis: Inhibition of myelination and induction of pro-inflammatory environment by FGF9","volume":"138","author":"Lindner","year":"2015","journal-title":"Brain"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Bonenfant, G., Meng, R., Shotwell, C., Badu, P., Payne, A.F., Ciota, A.T., Sammons, M.A., Berglund, J.A., and Pager, C.T. (2020). Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a Neuroblastoma Cell Line. Viruses, 12.","DOI":"10.3390\/v12050510"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:09:45Z","timestamp":1760159385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010091"],"URL":"https:\/\/doi.org\/10.3390\/v13010091","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]}}}