2017-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649043摘要：71 型腸病毒為新興致命性病毒，好發於亞太地區，輕症會造成手足口症，重症可引起腦脊髓炎、類小兒麻痺症癱瘓、甚或合併心肺衰竭休克猝死。截至目前，並無有效之藥物或疫苗可對抗。從我們先前動物研究中，已得知腸病毒71 型感染後可透過調控宿主的微核糖核酸(miR-141 與miR-146a)，使宿主關閉自身蛋白質合成機制，並抑制宿主干擾素合成而逃脫宿主免疫反擊，而促進了病毒的複製能力。因此，了解宿主與病毒交互作用，有助於發展有效之腸病毒71 型治療方法。T 細胞受器在辨識細胞內病原體和清除被感染的細胞扮演關鍵性角色。病毒感染能夠塑型局部與全身性T 細胞庫，適當T 細胞受器庫可用於攻擊71 型腸病毒達到防禦作用，然而，過度T 細胞受器庫反應可能會造成過當免疫反應而令宿主組織壞損並導致無法復原之後遺症。因此，調節T 細胞受器庫使宿主有適當的免疫反應，是發展免疫治療一項具潛能且可行策略。為了徹底瞭解 71 型腸病毒感染後宿主防禦機制以及病毒致病機轉，本計劃中，藉由新一代定序儀分析腸病毒71 型病人在感染後T 細胞受器庫的變化及此變化在致病機轉中的角色。之後，尋找過度放大之T 細胞受器族群，探討T 細胞受器庫之免疫角色及與疾病嚴重度的關聯性，並尋找可作為免疫治療之標的。<br> Abstract: Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly inthe Asia-Pacific region recently. EV71 infection causes typicalhand-foot-and-mouth disease, encephalomyelitis, poliomyelitis-like paralysis,sometimes combined with cardiopulmonary failure and sudden death or evenneurologic and psychiatric sequelae. Currently, there are no antivirals or vaccinesavailable against EV71. Thorough understanding of viral pathogenesis and hostdefense mechanisms against EV71 infection is mandatory for antiviral therapydevelopment. Previously we found EV71 can govern host protein synthesis,escape host immune attacks and further facilitate viral propagation by regulatinghost miRNAs.Immune response is the most important defense system, particularly on the virusinfection. T-cell receptor (TCR) plays a critical role in recognizing intracellularpathogens and initiating the destruction cascade of virus-infected cells. Virusinfection is found to shape the local and systemic T cell repertoire. The properresponse of TCR repertoire is necessary for immune attack against EV71 whileoverwhelming immune response may damage hosts and cause catastrophicsequelae. Hence, manipulation of TCR repertoire may be a potential strategy fordevelopment of immunotherapy against EV71.In this proposal, we would like to thoroughly explore the TCR repertoire ofvarious severities in EV71 patients and analyze critical elements for EV71pathogenesis by next generation sequencing (NGS) strategy. We intend todiscover the T cell immuno-repertoire patterns in EV71 infection and provided abig picture on EV71 pathogenesis and immune response by this strategy. We willhave thorough realization of EV71 pathogenesis through this proposal and theresults will shed light on development of therapeutic strategies for EV71infections.71 型腸病毒T 細胞免疫庫嚴重度致病機轉免疫治療EV71T-cell receptor (TCR)immune repertoireseveritypathogenesisimmunotherapy