PDF(Pubmed)
Abstract：
Tick-borne Encephalitis (TBE) is a zoonotic disease caused by the Tick-borne Encephalitis virus (TBEV), which affects the central nervous system of both humans and animals. Currently, there is no specific therapy for patients with TBE, with symptomatic treatment being the primary approach. In this study, the effects of minocycline (MIN), which is a kind of tetracycline antibiotic, on TBEV propagation and cellular protection in TBEV-infected cell lines were evaluated. Indirect immunofluorescence, virus titers, and RT-qPCR results showed that 48 h post-treatment with MIN, TBEV replication was significantly inhibited in a dose-dependent manner. In addition, the inhibitory effect of MIN on different TBEV multiplicities of infection (MOIs) in Vero cells was studied. Furthermore, the transcriptomic analysis and RT-qPCR results indicate that after incubation with MIN, the levels of TBEV and CALML4 were decreased, whereas the levels of calcium channel receptors, such as RYR2 and SNAP25, were significantly increased. MIN also regulated MAPK-ERK-related factors, including FGF2, PDGFRA, PLCB2, and p-ERK, and inhibited inflammatory responses. These data indicate that administering MIN to TBEV-infected cells can reduce the TBEV level, regulate calcium signaling pathway-associated proteins, and inhibit the MAPK-ERK signaling pathway and inflammatory responses. This research offers innovative strategies for the advancement of anti-TBEV therapy.
摘要：
蜱传脑炎（TBE）是由蜱传脑炎病毒（TBEV）引起的人畜共患疾病，影响人类和动物的中枢神经系统。目前,没有针对TBE患者的特定疗法，对症治疗是主要方法。在这项研究中,米诺环素（MIN）的作用，这是一种四环素抗生素，对TBEV感染的细胞系中的TBEV增殖和细胞保护进行了评估。间接免疫荧光，病毒滴度,RT-qPCR结果表明，用MIN处理48h后，TBEV复制以剂量依赖性方式被显著抑制。此外,研究了MIN对Vero细胞中不同TBEV感染复数（MOIs）的抑制作用。此外，转录组学分析和RT-qPCR结果表明，与MIN孵育后，TBEV和CALML4的水平降低，而钙通道受体的水平，如RYR2和SNAP25，均显著升高。MIN还调节MAPK-ERK相关因子，包括FGF2，PDGFRA，PLCB2和p-ERK,并抑制炎症反应。这些数据表明，向TBEV感染的细胞施用MIN可以降低TBEV水平，调节钙信号通路相关蛋白，抑制MAPK-ERK信号通路和炎症反应。这项研究为抗TBEV治疗的发展提供了创新的策略。
