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Unraveling the role of human microglia in tick-borne encephalitis virus infection: insights into neuroinflammation and viral pathogenesis

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    0602770 - BC 2025 RIV NL eng J - Journal Article
    Prančlová, Veronika - Nedvědová, Lenka - Kotounová, Eliška - Hönig, Václav - Dvořáková, Markéta - Davídková, Markéta - Bílý, Tomáš - Vancová, Marie - Růžek, Daniel - Palus, Martin
    Unraveling the role of human microglia in tick-borne encephalitis virus infection: insights into neuroinflammation and viral pathogenesis.
    Microbes and Infection. Roč. 26, č. 8 (2024), č. článku 105383. ISSN 1286-4579. E-ISSN 1769-714X
    R&D Projects: GA ČR(CZ) GA20-30500S; GA MŠMT(CZ) LX22NPO5103; GA MŠMT(CZ) LM2023050; GA MŠMT(CZ) EF18_046/0016045
    Research Infrastructure: Czech-BioImaging III - 90250
    Institutional support: RVO:60077344
    Keywords : 3-dimensional architecture * t-cells * replication * astrocytes * Tick-borne encephalitis virus * Primary human microglia * Cytokine/chemokine * Neuroinflammation * Viral strains
    OECD category: Virology
    Impact factor: 2.6, year: 2023 ; AIS: 0.671, rok: 2023
    Method of publishing: Open access
    Result website:
    https://doi.org/10.1016/j.micinf.2024.105383DOI: https://doi.org/10.1016/j.micinf.2024.105383

    Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudoeurorfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation. (c) 2024 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
    Permanent Link: https://hdl.handle.net/11104/0360064


     
     
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