Neurovirulence of Usutu virus in human fetal organotypic brain slice cultures partially resembles Zika and West Nile virus.
Humans
West Nile virus
/ pathogenicity
Zika Virus
/ pathogenicity
Brain
/ virology
Virus Replication
/ drug effects
Flavivirus
/ pathogenicity
Fetus
/ virology
Interferon-beta
/ pharmacology
Animals
Virulence
Organ Culture Techniques
Viral Tropism
Neurons
/ virology
Flavivirus Infections
/ virology
Zika Virus Infection
/ virology
Chlorocebus aethiops
Vero Cells
Flavivirus
Neurotropism & ex vivo brain model
Usutu virus
West Nile virus
Zika virus
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 Aug 2024
29 Aug 2024
Historique:
received:
18
03
2024
accepted:
23
08
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
29
8
2024
Statut:
epublish
Résumé
Usutu (USUV), West Nile (WNV), and Zika virus (ZIKV) are neurotropic arthropod-borne viruses (arboviruses) that cause severe neurological disease in humans. However, USUV-associated neurological disease is rare, suggesting a block in entry to or infection of the brain. We determined the replication, cell tropism and neurovirulence of these arboviruses in human brain tissue using a well-characterized human fetal organotypic brain slice culture model. Furthermore, we assessed the efficacy of interferon-β and 2'C-methyl-cytidine, a synthetic nucleoside analogue, in restricting viral replication. All three arboviruses replicated within the brain slices, with WNV reaching the highest titers, and all primarily infected neuronal cells. USUV- and WNV-infected cells exhibited a shrunken morphology, not associated with detectable cell death. Pre-treatment with interferon-β inhibited replication of all arboviruses, while 2'C-methyl-cytidine reduced only USUV and ZIKV titers. Collectively, USUV can infect human brain tissue, showing similarities in tropism and neurovirulence as WNV and ZIKV. These data suggest that a blockade to infection of the human brain may not be the explanation for the low clinical incidence of USUV-associated neurological disease. However, USUV replicated more slowly and to lower titers than WNV, which could help to explain the reduced severity of neurological disease resulting from USUV infection.
Identifiants
pubmed: 39209987
doi: 10.1038/s41598-024-71050-w
pii: 10.1038/s41598-024-71050-w
doi:
Substances chimiques
Interferon-beta
77238-31-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20095Subventions
Organisme : Lundbeck Foundation
ID : R359-2020-2287
Organisme : Lundbeck Foundation
ID : R359-2020-2287
Organisme : Dutch Research Council
ID : NWA 1160.1S.210
Pays : Netherlands
Informations de copyright
© 2024. The Author(s).
Références
Rocklöv, J. & Dubrow, R. Climate change: An enduring challenge for vector-borne disease prevention and control. Nat. Immunol. 21, 479–483 (2020).
pubmed: 32313242
pmcid: 7223823
doi: 10.1038/s41590-020-0648-y
Chang, C., Ortiz, K., Ansari, A. & Gershwin, M. E. The Zika outbreak of the 21st century. J. Autoimmun. 68, 1 (2016).
pubmed: 26925496
pmcid: 7127657
doi: 10.1016/j.jaut.2016.02.006
Tahotná, A., Brucknerová, J. & Brucknerová, I. Zika virus infection from a newborn point of view. TORCH or TORZiCH?. Interdiscip. Toxicol. 11, 241 (2018).
pubmed: 31762675
doi: 10.2478/intox-2018-0023
Muñoz, L. S., Parra, B. & Pardo, C. A. Neurological implications of Zika virus infection in adults. J. Infect. Dis. 216, S897 (2017).
pubmed: 29267923
pmcid: 5853915
doi: 10.1093/infdis/jix511
Historic Data (1999–2022) | West Nile Virus | CDC. at < https://www.cdc.gov/westnile/statsmaps/historic-data.html >
Surveillance, prevention and control of West Nile virus and Usutu virus infections in the EU/EEA. EFSA Supporting Publications 20, (2023).
Vilibic-Cavlek, T. et al. Epidemiology of usutu virus: The European scenario. Pathogens 9, 1–19 (2020).
doi: 10.3390/pathogens9090699
Gill, C. M. et al. Usutu virus disease: A potential problem for North America?. J. Neurovirol. 26, 149–154 (2020).
pubmed: 31858483
doi: 10.1007/s13365-019-00818-y
Clé, M. et al. Neurocognitive impacts of arbovirus infections. J. Neuroinflammation 17, (2020).
Simonin, Y. et al. Human usutu virus infection with atypical neurologic presentation, Montpellier, France, 2016. Emerg. Infect. Dis. 24, 875 (2018).
pubmed: 29664365
pmcid: 5938765
doi: 10.3201/eid2405.171122
Grottola, A. et al. Usutu virus infections in humans: A retrospective analysis in the municipality of Modena, Italy. Clin. Microbiol. Infect. 23, 33–37 (2017).
pubmed: 27677699
doi: 10.1016/j.cmi.2016.09.019
Jensen, C. & Teng, Y. Is it time to start transitioning from 2D to 3D cell culture?. Front. Mol. Biosci. 7, 513823 (2020).
doi: 10.3389/fmolb.2020.00033
Walczak, P. A., Perez-Esteban, P., Bassett, D. C. & Hill, E. J. Modelling the central nervous system: tissue engineering of the cellular microenvironment. Emerg. Top Life Sci. 5, 507–517 (2021).
pubmed: 34524411
pmcid: 8589431
doi: 10.1042/ETLS20210245
Setia, H. & Muotri, A. R. Brain organoids as a model system for human neurodevelopment and disease. Semin. Cell Dev. Biol. 95, 93–97 (2019).
pubmed: 30904636
pmcid: 6755075
doi: 10.1016/j.semcdb.2019.03.002
Jucker, M. The benefits and limitations of animal models for translational research in neurodegenerative diseases. Nat. Med. 16, 1210–1214 (2010).
pubmed: 21052075
doi: 10.1038/nm.2224
Rashidi, A. S. et al. Herpes simplex virus infection induces necroptosis of neurons and astrocytes in human fetal organotypic brain slice cultures. J. Neuroinflammation 21, 1–16 (2024).
doi: 10.1186/s12974-024-03027-5
Bulstrode, H. et al. Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells. Neuron 110, 3936-3951.e10 (2022).
pubmed: 36174572
pmcid: 7615581
doi: 10.1016/j.neuron.2022.09.002
Lin, M. Y. et al. Zika virus infects intermediate progenitor cells and post-mitotic committed neurons in human fetal brain tissues. Sci. Rep. 7, 1–8 (2017).
Croft, C. L., Futch, H. S., Moore, B. D. & Golde, T. E. Organotypic brain slice cultures to model neurodegenerative proteinopathies. Mol. Neurodegener. 14, 1–11 (2019).
doi: 10.1186/s13024-019-0346-0
Alaylioğlu, M., Dursun, E., Yilmazer, S. & Gezen Ak, D. A Bridge between in vitro and in vivo studies in neuroscience: Organotypic brain slice cultures. Arch. Neuropsychiatry 57, 333 (2020).
Kelley, K. W. & Pașca, S. P. Human brain organogenesis: Toward a cellular understanding of development and disease. Cell 185, 42–61 (2022).
pubmed: 34774127
doi: 10.1016/j.cell.2021.10.003
Witusik, M. et al. Successful elimination of non-neural cells and unachievable elimination of glial cells by means of commonly used cell culture manipulations during differentiation of GFAP and SOX2 positive neural progenitors (NHA) to neuronal cells. BMC Biotechnol. 8, 1–12 (2008).
doi: 10.1186/1472-6750-8-56
Dráberová, E. et al. Class III β-tubulin is constitutively coexpressed with glial fibrillary acidic protein and Nestin in midgestational human fetal astrocytes: Implications for phenotypic identity. J. Neuropathol. Exp. Neurol. 67, 341–354 (2008).
pubmed: 18379434
doi: 10.1097/NEN.0b013e31816a686d
Zecevic, N. Specific characteristic of radial glia in the human fetal telencephalon. Glia 48, 27–35 (2004).
pubmed: 15326612
doi: 10.1002/glia.20044
Bhaduri, A. et al. Cell stress in cortical organoids impairs molecular subtype specification. Nature 578, 142 (2020).
pubmed: 31996853
pmcid: 7433012
doi: 10.1038/s41586-020-1962-0
Eze, U. C., Bhaduri, A., Haeussler, M., Nowakowski, T. J. & Kriegstein, A. R. Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nat. Neurosci. 24, 584–594 (2021).
pubmed: 33723434
pmcid: 8012207
doi: 10.1038/s41593-020-00794-1
Imre, G. Cell death signalling in virus infection. Cell Signal 76, 109772 (2020).
pubmed: 32931899
pmcid: 7486881
doi: 10.1016/j.cellsig.2020.109772
Fricker, M., Tolkovsky, A. M., Borutaite, V., Coleman, M. & Brown, G. C. Neuronal cell death. Physiol. Rev. 98, 813–880 (2018).
pubmed: 29488822
pmcid: 5966715
doi: 10.1152/physrev.00011.2017
Kalil, A. C. et al. Use of interferon-α in patients with West Nile encephalitis: Report of 2 cases. Clin. Infect. Dis. 40, 764–766 (2005).
pubmed: 15714427
doi: 10.1086/427945
Lewis, M. & Amsden, J. R. Successful treatment of West Nile virus infection after approximately 3 weeks into the disease course. Pharmacother. J. Human Pharmacol. Drug Ther. 27, 455–458 (2007).
doi: 10.1592/phco.27.3.455
Kasule, S. N., Gupta, S., Patron, R. L., Grill, M. F. & Vikram, H. R. Neuroinvasive West Nile virus infection in solid organ transplant recipients. Transplant Infect. Dis. 25, e14004 (2023).
doi: 10.1111/tid.14004
Winston, D. J. et al. Donor-derived west nile virus infection in solid organ transplant recipients: Report of four additional cases and review of clinical, diagnostic, and therapeutic features. Transplantation 97, 881 (2014).
pubmed: 24827763
pmcid: 5765745
doi: 10.1097/TP.0000000000000024
Sayao, A.-L. et al. Calgary experience with West Nile virus neurological syndrome during the late summer of 2003. Can. J. Neurol. Sci. 31, 194–203 (2004).
pubmed: 15198443
doi: 10.1017/S031716710005383X
Chan-Tack, K. M. & Forrest, G. Failure of interferon alpha-2b in a patient with West Nile virus meningoencephalitis and acute flaccid paralysis. Scand. J. Infect Dis. 37, 944–946 (2005).
pubmed: 16308241
doi: 10.1080/00365540500262690
Penn, R. G. et al. Persistent neuroinvasive West Nile virus infection in an Immunocompromised patient. Clin. Infect. Dis. 42, 680–683 (2006).
pubmed: 16447115
doi: 10.1086/500216
Benzaria, S. et al. 2′-C-Methyl branched pyrimidine ribonucleoside analogues: Potent inhibitors of RNA virus replication. Antivir. Chem. Chemother. 18, 225–242 (2007).
pubmed: 17907380
doi: 10.1177/095632020701800406
Julander, J. G. et al. Efficacy of 2′-C-methylcytidine against yellow fever virus in cell culture and in a hamster model. Antivir. Res. 86, 261 (2010).
pubmed: 20227442
doi: 10.1016/j.antiviral.2010.03.004
Historical data by year - West Nile virus seasonal surveillance. at < https://www.ecdc.europa.eu/en/west-nile-fever/surveillance-and-disease-data/historical >
Agliani, G. et al. Pathological features of West Nile and Usutu virus natural infections in wild and domestic animals and in humans: A comparative review. One Health 16, 100525 (2023).
pubmed: 37363223
pmcid: 10288044
doi: 10.1016/j.onehlt.2023.100525
Peng, B. H. & Wang, T. West Nile virus induced cell death in the central nervous system. Pathogens 8, 215 (2019).
pubmed: 31683807
pmcid: 6963722
doi: 10.3390/pathogens8040215
Pan, Y., Cheng, A., Wang, M., Yin, Z. & Jia, R. The dual regulation of apoptosis by flavivirus. Front. Microbiol. 12, 654494 (2021).
pubmed: 33841381
pmcid: 8024479
doi: 10.3389/fmicb.2021.654494
Salinas, S. et al. Deleterious effect of Usutu virus on human neural cells. PLoS Negl. Trop. Dis. 11, e0005913 (2017).
pubmed: 28873445
pmcid: 5600396
doi: 10.1371/journal.pntd.0005913
Yang, S. et al. Zika virus-induced neuronal apoptosis via increased mitochondrial fragmentation. Front. Microbiol. 11, 598203 (2020).
pubmed: 33424801
pmcid: 7785723
doi: 10.3389/fmicb.2020.598203
Vig, P. J. S. et al. Differential expression of genes related to innate immune responses in ex vivo spinal cord and cerebellar slice cultures infected with west Nile Virus. Brain Sci. 9, 1 (2018).
pubmed: 30586874
pmcid: 6356470
doi: 10.3390/brainsci9010001
Clarke, P. et al. Death receptor-mediated apoptotic signaling is activated in the brain following infection with west nile virus in the absence of a peripheral immune response. J. Virol. 88, 1080–1089 (2014).
pubmed: 24198425
pmcid: 3911655
doi: 10.1128/JVI.02944-13
Lim, S. M. et al. Characterization of the mouse neuroinvasiveness of selected European strains of West nile virus. PLoS One 8, 74575 (2013).
doi: 10.1371/journal.pone.0074575
Solomon, T., Ooi, M. H., Beasley, D. W. C. & Mallewa, M. West Nile encephalitis. BMJ: Br. Med. J. 326, 865 (2003).
doi: 10.1136/bmj.326.7394.865
Bai, F., Ashley Thompson, E., Vig, P. J. S. & Arturo Leis, A. Current understanding of West nile virus clinical manifestations, immune responses, neuroinvasion, and immunotherapeutic implications. Pathogens 8, 193 (2019).
pubmed: 31623175
pmcid: 6963678
doi: 10.3390/pathogens8040193
Bosanko, C. M. et al. West Nile virus encephalitis involving the substantia nigra: Neuroimaging and pathologic findings with literature review. Arch. Neurol. 60, 1448–1452 (2003).
pubmed: 14568817
doi: 10.1001/archneur.60.10.1448
Kelley, T. W., Prayson, R. A., Ruiz, A. I., Isada, C. M. & Gordon, S. M. The neuropathology of West Nile virus meningoencephalitis: A report of two cases and review of the literature. Am. J. Clin. Pathol. 119, 749–753 (2003).
pubmed: 12760295
doi: 10.1309/PU4R76JJMG1F81RP
Armah, H. B. et al. Systemic distribution of West Nile virus infection: Postmortem immunohistochemical study of six cases. Brain Pathol. 17, 354–362 (2007).
pubmed: 17610522
pmcid: 8095553
doi: 10.1111/j.1750-3639.2007.00080.x
Guarner, J. et al. Clinicopathologic study and laboratory diagnosis of 23 cases with West Nile virus encephalomyelitis. Hum. Pathol. 35, 983–990 (2004).
pubmed: 15297965
doi: 10.1016/j.humpath.2004.04.008
Goldsmith, C. et al. Fatal West nile virus encephalitis in a renal transplant recipient. Am. J. Clin. Pathol. 121, 26–31 (2004).
pubmed: 14750237
doi: 10.1309/G23CP54DAR1BCY8L
Schafernak, K. T. & Bigio, E. H. West Nile virus encephalomyelitis with polio-like paralysis & nigral degeneration. Can. J. Neurol. Sci. 33, 407–410 (2006).
pubmed: 17168167
doi: 10.1017/S0317167100005370
Reddy, P. et al. West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation. Bone Marrow Transplant 33, 109–112 (2004).
pubmed: 14566328
doi: 10.1038/sj.bmt.1704293
Penn, R. G. et al. Persistent neuroinvasive west nile virus infection in an immunocompromised patient. Clin. Antivir. Dis. 42, 680–683 (2006).
doi: 10.1086/500216
Omalu, B. I., Shakir, A. A., Wang, G., Lipkin, W. I. & Wiley, C. A. Fatal fulminant pan-meningo-polioencephalitis due to west nile virus. Brain Pathol. 13, 465–472 (2003).
pubmed: 14655752
doi: 10.1111/j.1750-3639.2003.tb00477.x
Gaibani, P., Cavrini, F., Gould, E. A., Rossini, G. & Pierro, A. Comparative genomic and phylogenetic analysis of the first usutu virus isolate from a human patient presenting with neurological symptoms. PLoS One 8, 64761 (2013).
doi: 10.1371/journal.pone.0064761
Mumtaz, N. et al. Cell-line dependent antiviral activity of sofosbuvir against Zika virus. Antivir. Res. 146, 161–163 (2017).
pubmed: 28912011
doi: 10.1016/j.antiviral.2017.09.004
Toussi, S. S., Hammond, J. L., Gerstenberger, B. S. & Anderson, A. S. Therapeutics for COVID-19. Nat. Microbiol. 8, 771–786 (2023).
pubmed: 37142688
doi: 10.1038/s41564-023-01356-4
Schäfer, C. B., Gao, Z., De Zeeuw, C. I. & Hoebeek, F. E. Temporal dynamics of the cerebello-cortical convergence in ventro-lateral motor thalamus. J. Physiol. 599, 2055–2073 (2021).
pubmed: 33492688
doi: 10.1113/JP280455
Oude Munnink, B. B. et al. Genomic monitoring to understand the emergence and spread of Usutu virus in the Netherlands, 2016–2018. Sci. Rep. 10, 2798 (2020).
pubmed: 32071379
pmcid: 7029044
doi: 10.1038/s41598-020-59692-y
Vlaskamp, D. R. et al. First autochthonous human west nile virus infections in the Netherlands, July to August 2020. Eurosurveillance 25, 1–4 (2020).
doi: 10.2807/1560-7917.ES.2020.25.46.2001904
Langerak, T. et al. Transplacental Zika virus transmission in ex vivo perfused human placentas. PLoS Negl. Trop. Dis. 16, e0010359 (2022).
pubmed: 35442976
pmcid: 9060339
doi: 10.1371/journal.pntd.0010359
Kärber, G. Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 162, 480–483 (1931).
doi: 10.1007/BF01863914
Bankhead, P. et al. QuPath: Open source software for digital pathology image analysis. Sci. Rep. 7, 1–7 (2017).
doi: 10.1038/s41598-017-17204-5