腸病毒71型 (EV71)在臨床上可以造成輕微手足口症，疱疹性咽唊炎到嚴重的中樞神經病變像是腦膜炎，腦幹腦炎並進一步導致死亡。然而，目前為止，臨床上沒有有效的藥物來治療腸病毒的感染。本實驗評估poly IC和ribavirin對於腸病毒感染人類神經細胞株的影響。首先，我們選用人類神經細胞 (SK-N-SH) 和人類神經膠細胞 (U118MG) 建立EV71的細胞感染模式，EV71皆可以在這二株細胞中感染且產生細胞病理效應，並造成細胞走向凋亡，進一步用免疫螢光染色也可以在細胞質中偵測出EV71抗原。除了直接造成細胞的傷害，EV71感染神經細胞也會產生細胞激素巨噬細胞移動抑制因子 (MIF)和介白素-8 (IL-8)釋放，並且隨時間和病毒量成正比。建立完細胞感染模式之後，我們進一步評估poly IC和ribavirin對腸病毒的抑制效果，poly IC可抑制EV71感染SK-N-SH，但對於感染U118MG的EV71則是沒有抑制的能力，而ribavirin則對感染這二株神經細胞的EV71皆具抑制能力，但我們同時也發現ribavirin對SK-N-SH有較高的細胞毒性，除此之外，如果同時使用poly IC和ribavirin，則可以發現此二種藥物對於抑制EV71有加成的作用，即可以用較低的藥物濃度達到高濃度之下的抑制效果，由這些實驗結果可以推測，同時使用poly IC和ribavirin或許可以有效治療受EV71感染的病人。

Enterovirus 71 (EV71) is the main causative agent of hand-foot-mouth disease, herpangina and has been associated with severe neurological disease like meningitis, encephalitis resulting in high mortalities. There is no effective antiviral drug could be used to cure the infection of EV71. In this study, we choose the interferon inducer poly IC and ribavirin to evaluate their effects on EV71 infection of human neuron cells. First, we selected two neural cell lines, SK-N-SH and U118MG to set up an in vitro EV71 infection model. We found EV71 infection in both cell lines induced the formation of cytopathic effect. EV71 antigen was also detected in the cytoplasm of EV71-infected cells. In addition, inflammatory cytokines such as macrophage migration inhibitory factor and interleukin-8 were increased in EV71-infected cells in a dose- and time-dependent manner. Treatment of poly IC could reduce the viral titer and inflammatory cytokines and increase the cell viability in SK-N-SH but not in U118MG cells. Ribavirin, on the other hand, possesses antiviral activity in both cell lines against EV71 infection. However, higher cytotoxicity of ribavirin in SK-N-SH was observed. Nevertheless, Synergenic effect of the combination usage of poly IC and ribavirin against EV71 infection of neural cells was found. Therefore, the cytotoxicity of ribavirin could be reduced by the combination usage of poly-IC. These results suggest the combination usage of interferon or its inducer and ribavirin in EV71 infection may worth to be used in patients.

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