Minocycline Inhibits Tick-Borne Encephalitis Virus and Protects Infected Cells via Multiple Pathways
Mengtao Cao,
Wei Yang,
Jintao Yang,
Yanli Zhao,
Xiaoyu Hu,
Xiaoli Xu,
Jing Tian,
Yue Chen,
Hongxia Jiang,
Ruiwen Ren,
Chunyuan Li
Affiliations
Mengtao Cao
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
Wei Yang
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Jintao Yang
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Yanli Zhao
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Xiaoyu Hu
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
Xiaoli Xu
Instrument Analysis & Research Center, South China Agricultural University, Guangzhou 510642, China
Jing Tian
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
Yue Chen
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
Hongxia Jiang
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Ruiwen Ren
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
Chunyuan Li
Center for Disease Control and Prevention of Southern Theater Command, Guangzhou 510507, China
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.
