| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 101 === Enterovirus 71 (EV71) is a single-stranded RNA virus belonging to the Picornaviridae family. EV71 is known to cause hand, foot and mouth disease in young children and has been implicated in severe neurological manifestations. It has been known that many viruses in picornaviridae induce endoplasmic reticulum (ER) stress but the mechanism remains unknown. Inositol-requiring enzyme 1 (IRE1) plays an important role in unfolded protein response. In our group, we have demonstrated that EV71 could induce the increase of phosphorylated IRE1 followed by activating its downstream target, c-Jun N-terminal protein kinase (JNK). We proposed that EV71 modulates IRE1 pathway to benefit its replication and mature virus release . Thus, in this study, we tried to further investigate this regulatory mechanism. We observed that knockdown of IRE1 results in a decreased level of virus titer, which was due to the attenuated viral protein expression and viral RNA replication. Besides that, when cells were treated with JNK inhibitor in the early stage of infection or siRNA of JNK2 , virus titer and mature virus release were significantly decreased . However , addition of JNK inhibitor and QVDOPH ( caspase inhibitor ) at 5 h.p.i has no influence on virus replication but resulted in reduction of viral particle release .These results support our current hypothesis that IRE1-JNK2 pathway involved in EV71 - induced apoptosis , which in turn facilitate virus release .
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