Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005 Ceske Budejovice, Czech Republic; Faculty of Science, University of South Bohemia, CZ-37005 Ceske Budejovice, Czech Republic.
Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005 Ceske Budejovice, Czech Republic; Laboratory of Emerging Viral Infections, Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czech Republic.
Microbes Infect. 2024 Nov-Dec;26(8):105383. doi: 10.1016/j.micinf.2024.105383. Epub 2024 Jun 26.
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, Neudörfl 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.
蜱传脑炎病毒（TBEV）是一种嗜神经性正呼肠孤病毒，可导致中枢神经系统的严重感染。尽管神经元是主要的靶标，但 TBE 发病机制中小胶质细胞的特定参与尚未完全清楚。在这项研究中，研究了人类小胶质细胞对 TBEV 的易感性，重点研究了不同病毒株的产感染和不同免疫反应。我们研究了暴露于三种 TBEV 株（Hypr、Neudörfl 和 280）的原代人小胶质细胞和两种永生化小胶质细胞系，每种病毒株的毒力都不同。我们的结果表明，所有测试的小胶质细胞培养物均支持长期产感染，与病毒株无关。特别是，免疫反应因病毒株而异，如通过 Luminex 48 plex 测定定量的细胞因子和趋化因子（如 IP-10、MCP-1、IL-8 和 IL-6）的差异分泌所示。最毒力的菌株引发最高的细胞因子诱导。电子断层摄影术揭示了受感染的小胶质细胞的大量超微结构变化，尽管没有细胞病变效应。这些发现强调了人类小胶质细胞对 TBEV 的易感性，并揭示了病毒复制和免疫反应的菌株依赖性变化，突出了小胶质细胞在 TBEV 诱导的神经病理学中的复杂作用，并有助于更深入地了解 TBE 的发病机制和神经炎症。
