Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: implications for CNS complications

Schultz, V. et al. (2021) Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: implications for CNS complications. Glia, 69(8), pp. 2023-2036. (doi: 10.1002/glia.24010) (PMID:33942402)

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Abstract

Some children with proven intrauterine Zika virus (ZIKV) infection who were born asymptomatic subsequently manifested neurodevelopmental delays, pointing to impairment of development perinatally and postnatally. To model this, we infected postnatal day (P) 5–6 (equivalent to the perinatal period in humans) susceptible mice with a mammalian cell‐propagated ZIKV clinical isolate from the Brazilian outbreak in 2015. All infected mice appeared normal up to 4 days post‐intraperitoneal inoculation (dpi), but rapidly developed severe clinical signs at 5–6 dpi. All nervous tissue examined at 5/6 dpi appeared grossly normal. However, anti‐ZIKV positive cells were observed in the optic nerve, brain, and spinal cord; predominantly in white matter. Co‐labeling with cell type specific markers demonstrated oligodendrocytes and astrocytes support productive infection. Rarely, ZIKV positive neurons were observed. In spinal cord white matter, which we examined in detail, apoptotic cells were evident; the density of oligodendrocytes was significantly reduced; and there was localized microglial reactivity including expression of the NLRP3 inflammasome. Together, our observations demonstrate that a clinically relevant ZIKV isolate can directly impact oligodendrocytes. As primary oligodendrocyte cell death can lead later to secondary autoimmune demyelination, our observations may help explain neurodevelopmental delays in infants appearing asymptomatic at birth and commend lifetime surveillance.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barrie, Mrs Jennifer and Schultz, Dr Verena and Donald, Dr Claire and Willison, Professor Hugh and Barnett, Professor Susan and Anderson, Professor Jim and Linington, Professor Christopher and Edgar, Professor Julia and Crawford, Colin and Kohl, Professor Alain and Mullin, Mrs Margaret
Authors: Schultz, V., Barrie, J. A., Donald, C. L., Crawford, C. L., Mullin, M., Anderson, T. J., Solomon, T., Barnett, S. C., Linington, C., Kohl, A., Willison, H. J., 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:Glia
Publisher:Wiley
ISSN:0894-1491
ISSN (Online):1098-1136
Published Online:04 May 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Glia 69(8): 2023-2036
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173101ZikaPLANHugh WillisonEuropean Commission (EC)Willison, Professor HughIII - Immunology
172663response to MRC ZIKA callHugh WillisonMedical Research Council (MRC)MC_PC_15105III - Immunology
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
172580The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1III-MRC-GU Centre for Virus Research
172913Zika virus- GBS: a joint Brazil-Colombia-UK infrastrucure projectHugh WillisonWellcome Trust (WELLCOTR)203680/Z/16/ZIII - Immunology
165079The 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