CW-33與干擾素β結合使用抑制腸病毒71型之功效

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題名:	CW-33與干擾素β結合使用抑制腸病毒71型之功效 Combined treatment of CW-33 and interferon beta inhibits on enterovirus 71
作者:	陳奕潔;I-Chieh Chen
貢獻者:	醫學檢驗生物技術學系碩士班
關鍵詞:	腸病毒71型;Enterovirus 71
日期:	2013-08-01
上傳時間:	2013-10-02 11:27:20 (UTC+8)
出版者:	中國醫藥大學
摘要:	腸病毒71型(EV71)屬於小核醣核酸病毒(Picornaviridae)家族，經由腸胃道或呼吸道等傳染途徑感染宿主，造成幼年兒童併發手足口症和中樞神經系統疾病。EV71 2A 蛋白?能切割多聚蛋白，使其產生功能性和結構性的蛋白，此外也會降低干擾素受體，具有擷抗干擾素訊號傳遞。目前為止沒有有效抗腸病毒71 型的藥物和疫苗被報導過。 ?喃??衍生類(furoquinolone)具有抗微生物、抗癌活性及抗病，本實驗室從系列?喃??中間合成衍生化合物中篩選出CW33 具有抗病毒活性。本實驗研究目的為探討抗腸病毒71 型活性，在感染EV71 的人類橫紋肌瘤細胞株(RD)在單獨處理CW33 或合併處理IFN-β 及其調查協同機制。單獨1000U/ml IFN-β 時會減少EV71（MOI=0.1）引起的細胞病變效應（CPE），但不是在MOI=0.5 和1，然而EV71 也會抑制p-STAT1-S727 的回復。單獨使用CW33 在高劑量125μM 情況下，處理EV71（MOI=1）時，對HeLa-G2AwtR 抑制效果為74%。協同治療CW-33 與100U/ml IFN-β 顯示更有淺力在減少EV71 所引起的CPE 現象和病毒產率在MOI=1 時，相較於單獨處理CW-33。協同125μM CW33 與100U/ml IFN-β 會抑制EV71 所誘發的NF-κB 報導基因活性，以及回復p-STAT1-Tyr701 的表現量。結果指出CW33 協同作用IFNβ 所引起的抗EV71。 Enterovirus 71 (EV71) is a member of human enterovirus genus in the Picornaviridae family, infecting human via the gastrointestinal and respiratory tracts as well as causing foot and mouth diseases and even central nervous system diseases in young children. Of EV71 proteins, 2A protease cleaves viral polyproteins to release structural and nonstructural proteins, redcuing interferon receptor along with anti-interferon signaling. No specific agents and vaccines against EV71 has been proved. Since furan quinoline derivative (furoquinolone) has anti-microbial, anti-cancer and anti-viral activities, our laboratory identified antiviral activity of CW-33 from screening the series of furan intermediate synthesized quinoline derivatives. The study aimed to explore anti-EV71 actions of CW-33 alone or combined with IFNβ as well as investigated the synergistic mechanism(s) against EV71 in human rhabdomyosarcoma (RD) cells. IFNβ alone at 1000 U/ml reduced EV71-induced cytopathic effect (CPE) at an MOI of 0.1, but not MOIs of 0.5 and 1, in which EV71 significantly suppressed the phosphorylated levels of STAT1 Ser727 in response to IFNβ. CW-33 alone at 125μM significantly inhibited EV71 replication (MOI=1) by 74% decrease in a FRET assay using GFP-2A recognition site-RFP expressing cells. Combined treatment of CW-33 with 100U/ml IFN-β showed more potential efficacy on reducing EV71-induced CPE and viral yields at an MOI of 1 in vitro compared to CW-33 alone. 125μM CW-33 combined with 100 U/ml IFN-β inhibited EV71-induced NF-κB signaling pathway using dual reporter assay as well as rescued the phosphorylated level of STAT1 Tyr701. The results indicated the synergistic action of CW-33 combined with IFNβ against EV71.
顯示於類別:	[醫學檢驗生物技術學系暨碩士班 ] 博碩士論文

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