標題: Cyclooxygenase-2 facilitates dengue virus replication and serves as a potential target for developing antiviral agents
作者: Lin, Chun-Kuang
Tseng, Chin-Kai
Wu, Yu-Hsuan
Liaw, Chih-Chuang
Lin, Chun-Yu
Huang, Chung-Hao
Chen, Yen-Hsu
Lee, Jin-Ching
生醫工程研究所
Institute of Biomedical Engineering
公開日期: 20-Mar-2017
摘要: Cyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice. Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E-2 (PGE(2)) production in human hepatoma Huh-7 cells. The exogenous expression of COX-2 or PGE2 treatment dose-dependently enhanced DENV-2 replication. In contrast, COX-2 gene silencing and catalytic inhibition sufficiently suppressed DENV-2 replication. In an ICR suckling mouse model, we identified that the COX-2 inhibitor NS398 protected mice from succumbing to life-threatening DENV-2 infection. By using COX-2 promoter-based analysis and specific inhibitors against signaling molecules, we identified that NF-kappa B and MAPK/JNK are critical factors for DENV-2-induced COX-2 expression and viral replication. Altogether, our results reveal that COX-2 is an important factor for DENV replication and can serve as a potential target for developing therapeutic agents against DENV infection.
URI: http://dx.doi.org/10.1038/srep44701
http://hdl.handle.net/11536/144620
ISSN: 2045-2322
DOI: 10.1038/srep44701
期刊: SCIENTIFIC REPORTS
Volume: 7
起始頁: 0
結束頁: 0
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