Zika virus infection leads to demyelination and axonal injury in mature CNS cultures

Schultz, V. et al. (2021) Zika virus infection leads to demyelination and axonal injury in mature CNS cultures. Viruses, 13(1), 91. (doi: 10.3390/v13010091) (PMID:33440758) (PMCID:PMC7827345)

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Abstract

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. 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—which is critical for saltatory conduction and neuronal function—has 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barrie, Mrs Jennifer and Schultz, Dr Verena and Da Silva Filipe, Dr Ana and Donald, Dr Claire and Willison, Professor Hugh and Barnett, Professor Susan and Linington, Professor Christopher and Edgar, Professor Julia and McCanney, George and Johnson, Miss Natasha and Gu, Dr Quan and Kohl, Professor Alain and Cumberworth, Miss Stephanie
Creator Roles:
Schultz, V.Conceptualization, Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft, Writing – review and editing
Cumberworth, S. L.Conceptualization, Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – review and editing
Gu, Q.Formal analysis, Investigation, Methodology, Software, Visualization, Writing – review and editing
Johnson, N.Investigation, Writing – review and editing
Donald, C. L.Investigation, Writing – review and editing
McCanney, G. A.Investigation, Writing – review and editing
Barrie, J. A.Methodology, Writing – review and editing
Da Silva Filipe, A.Methodology, Writing – review and editing
Linington, C.Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review and editing
Willison, H. J.Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – review and editing
Edgar, J. M.Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – review and editing
Barnett, S.Data curation, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing
Barnett, S. C.Conceptualization
Kohl, A.Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing
Authors: Schultz, V., Cumberworth, S. L., Gu, Q., Johnson, N., Donald, C. L., McCanney, G. A., Barrie, J. A., Da Silva Filipe, A., Linington, C., Willison, H. J., Edgar, J. M., Barnett, S. C., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Viruses
Publisher:MDPI
ISSN:1999-4915
ISSN (Online):1999-4915
Copyright Holders:Copyright: © 2021 by the authors
First Published:First published in Viruses 13(1):91
Publisher Policy:Reproduced under a Creative Commons license
Data DOI:10.5525/gla.researchdata.1049

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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
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research
190660MRC Doctoral Training Grant 2013/14 and 2014/15George BaillieMedical Research Council (MRC)MR/K501335/1MVLS - Graduate School
172913Zika virus- GBS: a joint Brazil-Colombia-UK infrastrucure projectHugh WillisonWellcome Trust (WELLCOTR)203680/Z/16/ZIII - Immunology