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標題: | 微核醣核酸於71型腸病毒感染中對病毒複製和宿主免疫反應的影響 The impacts of miRNAs on viral replication and host immune responses in enterovirus 71 infection |
作者: | Bing-Ching Ho 何炳慶 |
指導教授: | 李君男(Chun-Nan Lee) |
關鍵字: | 微核醣核酸,微核醣核酸141,微核醣核酸146a,轉譯機制轉換,干擾素反應, MicroRNAs,miR-141,miR-146a,translation switch,interferon responses, |
出版年 : | 2011 |
學位: | 博士 |
摘要: | 病毒感染過程中,病毒與宿主間具有複雜的相互作用。病毒感染過程會依賴宿主轉譯蛋白質機制,藉此完成其生命週期並進行其致病機制。而在宿主方面,會因應產生一系列免疫反應來消除病毒的傳播。微核醣核酸(miRNAs)是近來發現的一類小片段、非蛋白編碼的核醣核酸,可藉由內源性RNA干擾方式來調控廣泛的生物功能,其中包括宿主與病毒的相互作用。於本論文中,我們觀察微核醣核酸於71型腸病毒感染前後表現量的差異,挑選了兩個在病毒感染過程中扮演重要角色的微核醣核酸 (miR-141與miR-146a)。miR-141為71型腸病毒感染細胞前後差異最顯著的微核醣核酸,可作用於轉譯起始因子4E,並關閉宿主的蛋白質合成,促進轉譯機制由cap-dependent轉譯轉換至cap-independent轉譯。miR-146a為另一個細胞受病毒感染而誘發的微核醣核酸,miR-146a可藉由3’非編碼區配對,進一步抑制兩個干擾素相關的蛋白質TRAF6和IRAK1表現。據研究指出,抑制TRAF6和IRAK1的表現會降低宿主干擾素反應。綜合以上結果,我們推測71型腸病毒可能是藉由調控上述兩個微核醣核酸來關閉宿主蛋白質合成並逃避宿主的抗病毒作用,進而有利於進行病毒的複製。 Virus processes complicated interactions with the host in virus infection. Virus relay on the host translation machinery to complete their life cycles and cause viral pathogenesis. In contrast, host utilizes immune system to eliminate virus spread. MicroRNAs (miRNAs) are a recently discovered class of small non-protein-coding RNAs that may act via endogenous RNA interference to govern a wide range of biological functions including host-virus interaction. In this thesis, we identified two miRNAs, miR-141 and miR-146a, which play significant roles in virus-host interactions. miR-141, the most up-regulated miRNA, targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis and promotes the switch from cap-dependent to cap-independent translation. miR-146a, the other up-regulated miRNA, suppressed two interferon-associated proteins, TRAF6 and IRAK1, through pairing to their 3’ untranslated regions. It was documented that suppression of TRAF6 and IRAK1 resulted in attenuation of host interferon responses. We hypothesized that EV71 might shutoff of host protein synthesis and escape host antiviral activity through regulation of the two miRNAs, and created a beneficial environment for its replication. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48557 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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