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

Cumberworth, S. L. et al. (2017) Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected. Acta Neuropathologica Communications, 5, 50. (doi:10.1186/s40478-017-0450-8) (PMID:28645311) (PMCID:PMC5481922)

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Abstract

The 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barrie, Mrs Jennifer and Schultz, Dr Verena and Brennan, Dr Benjamin and Willison, Professor Hugh and Barnett, Professor Susan and Linington, Professor Christopher and Cunningham, Dr Madeleine and Edgar, Dr Julia and Kohl, Professor Alain and Cumberworth, Miss Stephanie
Authors: Cumberworth, S. L., Barrie, J. A., Cunningham, M. E., Gomes de Figueiredo, D. P., Schultz, V., Wilder-Smith, A. J., Brennan, B., Pena, L. J., de Oliveira França, R. F., Linington, C., Barnett, S. C., Willison, H. J., Kohl, A., and Edgar, J. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Acta Neuropathologica Communications
Publisher:BioMed Central
ISSN:2051-5960
ISSN (Online):2051-5960
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Acta Neuropathologica Communications 5:50
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
708681The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1MVLS III - CENTRE FOR VIRUS RESEARCH
739041Zika virus- GBS: a joint Brazil-Colombia-UK infrastrucure projectHugh WillisonWellcome Trust (WELLCOTR)203680/Z/16/ZIII -IMMUNOLOGY
544031The structural and functional diversity of anti-glycolipid antibody repertoires and their nerve binding domains in human autoimmune neuropathyHugh WillisonWellcome Trust (WELLCOTR)092805/Z/10/ZIII -IMMUNOLOGY
736191ZikaPLANHugh WillisonEuropean Commission (EC)734584III -IMMUNOLOGY

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