Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Ethics Statement
2.2. Cell Culture
2.3. Viruses and Infection of Neural Cultures with ZIKV
2.4. RNA Isolation and Purification
2.5. RT-PCR for Receptor Expression Detection
2.6. RNA Sequencing and Data Analysis
2.7. CCL5 Treatment during Culture Development
2.8. Supernatant Transfer
2.9. IF Analysis of CNS Cultures
2.10. Image Capture and Analysis
2.11. Statistics
3. Results
3.1. Myelinated, Mature CNS Cultures Are Vulnerable to ZIKV Infection
3.2. Timing of Myelin Damage and Axonal Injury Following ZIKV Infection
3.3. Transcriptome Analysis of Mature, ZIKV-Infected CNS Cultures
3.4. CCL5 Disrupts Developmental Myelination
3.5. Transfer of UV-Treated Media from Infected Cultures Did Not Lead to Myelin and Axonal Damage in CNS Cultures
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Gene | Ref | Primer 1 | Primer 2 | Start | End | Size (bp) | Tm | Source |
---|---|---|---|---|---|---|---|---|
Axl | NM_009465.4 | CCCCTGAGAACGTTAGCG | CGATCTACCATGACGTCTCGT | 1244 | 1835 | 591 | 56 | Pierce et al. 2008 [65] |
Tyro3 | NM_019392.2 | CGATCTCCAGCTACAACGC | TAAGGCCTGAGTCGGTACG | 950 | 1261 | 311 | 56 | Pierce et al. 2008 [65] |
Mertk | NM_008587.1 | CTGCACAGTGAGAATCGCG | GCTTGTGTAGA CTCGGTCCG | 1402 | 2371 | 969 | 56 | Pierce et al. 2008 [65] |
Havcr2 (Tim-3) | NM_134250.2 | TTAGACATCAAAGCAGCCAAGG | CAGCAGAGACTCCCACTCCAAT | 452 | 677 | 225 | 56 | He et al. 2009 [66] |
Havcr1 (Tim-1) | NM_001166631.1 | TGCTGCTACTGCTCCTTGTG | AACCACGCTTAGAGATGCTGA | 841 | 923 | 83 | 60 | Designed for this study |
Cd209a (DC-SIGN) | NM_133238.5 | GAGATGACGGCTGGAATGAC | AGATGGTGGAGGGAGTTGG | 710 | 817 | 108 | 60 | Designed for this study |
18S | NR_003278.1 | GACTCAACACGGGAAACCTC | TAACCAGACAAATCGCTCCAC | 1245 | 1369 | 124 | 60 | Bryden et al. 2020 [67] |
Timd4 (Tim-4) | NM_178759.4 | GGATAGGGAATGGCACTTGA | CAACCAGACAGGACCCACA | 1070 | 1172 | 103 | 60 | Designed for this study |
Gene | Expression at DIV 18 ± 2 | Expression at DIV 26 ± 2 |
---|---|---|
Axl | + | + |
Tyro3 | + | + |
Mertk | + | + |
Havcr2 (Tim-3) | + | + |
Havcr1 (Tim-1) | − | − |
Cd209a (DC-SIGN) | − | − |
Timd4 (Tim-4) | − | − |
Appendix B
Gene | Description | Log2FC | q-Value |
---|---|---|---|
5430419D17Rik | RIKEN cDNA 5430419D17 gene | 1.349822632 | 0.013727 |
Ptgds | Prostaglandin D2 synthase which is highly expressed in mouse brain tissue | 1.159369699 | 6.11 × 10−13 |
Dcd dopa decarboxylase | Dcd dopa decarboxylase | 0.798480908 | 0.001119 |
Prdm16os | Prdm16 opposite strand transcript | 0.783089832 | 0.047293 |
C1s1 | Complement component 1, subcomponent 1 | 0.781542798 | 0.032348 |
Sult1a1 | Sulfotransferase family 1A, phenol-preferring, member 1 | 0.735819031 | 0.039275 |
Lyz2 | Lysozyme C-2 precursor | 0.67208358 | 0.000261 |
Abca9 | ATP-binding cassette, sub-family A (ABC1), member 9 | 0.624110509 | 0.032074 |
Lrriq1 | Leucine-rich repeats and IQ motif containing 1 | 0.548544221 | 0.040768 |
Aldh6a1 | Aldehyde dehydrogenase family 6, subfamily A1 | 0.504553732 | 0.013727 |
Hacd4 | 3-hydroxyacyl-CoA dehydratase 4 | 0.479419852 | 0.040768 |
Prom1 | Prominin 1 | 0.47554711 | 0.042655 |
Ccdc3 | Coiled-coil domain containing 3 | 0.453373011 | 0.04515 |
Lims2 | LIM zinc finger domain containing 2 | −0.474966406 | 0.029954 |
Dbx2 | Developing brain homeobox 2 | −0.589232159 | 0.001985 |
Tubb6 | tubulin, beta 6 class V | −0.718924133 | 0.028927 |
Cited1 | Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 | −0.823628338 | 0.032684 |
Kif23 | Kinesin family member 23 | −0.961728063 | 0.040768 |
Gm35455 | Uncharacterized | −1.272445743 | 0.042655 |
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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.; et al. Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures. Viruses 2021, 13, 91. https://doi.org/10.3390/v13010091
Schultz V, Cumberworth SL, Gu Q, Johnson N, Donald CL, McCanney GA, Barrie JA, Da Silva Filipe A, Linington C, Willison HJ, et al. Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures. Viruses. 2021; 13(1):91. https://doi.org/10.3390/v13010091
Chicago/Turabian StyleSchultz, Verena, Stephanie L. Cumberworth, Quan Gu, Natasha Johnson, Claire L. Donald, George A. McCanney, Jennifer A. Barrie, Ana Da Silva Filipe, Christopher Linington, Hugh J. Willison, and et al. 2021. "Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures" Viruses 13, no. 1: 91. https://doi.org/10.3390/v13010091
APA StyleSchultz, 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., & Kohl, A. (2021). Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures. Viruses, 13(1), 91. https://doi.org/10.3390/v13010091