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 Gu, Dr Quan and Willison, Professor Hugh and Barnett, Professor Susan and Da Silva Filipe, Dr Ana and Linington, Professor Christopher and Schultz, Dr Verena and Edgar, Professor Julia and McCanney, George and Donald, Dr Claire and Kohl, Professor Alain and Johnson, Miss Natasha 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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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