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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林宜玲 | |
| dc.contributor.author | Hsin-Ping Chiu | en |
| dc.contributor.author | 邱馨平 | zh_TW |
| dc.date.accessioned | 2021-06-17T04:30:56Z | - |
| dc.date.available | 2018-09-04 | |
| dc.date.copyright | 2018-09-04 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-10 | |
| dc.identifier.citation | 1. Gao G, Guo X, Goff SP. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science. 2002;297(5587):1703-6.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70554 | - |
| dc.description.abstract | CCCH型鋅指抗病毒蛋白質 (CCCH-type zinc-finger antiviral protein, ZAP) 是一可抑制多種病毒感染的宿主因子，其利用誘發RNA降解、抑制蛋白質轉譯及加強先天性免疫反應等細胞機制達成抗病毒的目標。目前為止，黃質病毒屬中只有黃熱病毒被報導對ZAP具有抵抗性；於本篇研究中，我們探討人類ZAP (ZAP-L及ZAP-S異構體) 對於其他黃質病毒，包括日本腦炎病毒 (Japanese encephalitis virus, JEV)、登革病毒 (dengue virus, DENV) 和茲卡病毒 (Zika virus, ZIKV) 之抗病毒潛力及抗病毒機制。過量表現ZAP的細胞可抑制JEV的感染，反之若降低細胞內生性ZAP表現，JEV的複製則會增加；然而過量表現ZAP的細胞並無顯著抑制DENV及ZIKV之效果。ZAP會抑制JEV的轉譯，並且吸引三端到五端RNA外切體複合物執行JEV RNA之降解；此外ZAP的鋅指結構區域，對於其辨識目標RNA和其抗病毒活性是必需的。JEV RNA的三端非轉譯區域，尤其是帶有啞鈴型態RNA結構和高比例CG雙核苷酸之第二功能區 (domain II)，會被ZAP所辨識，並且對ZAP具感受性。綜合以上所述，我們發現JEV是第一個被ZAP抑制的黃質病毒，ZAP可藉由特異辨識JEV RNA進而抵抗JEV感染，在細胞中扮演內源性抗病毒因子的角色。 | zh_TW |
| dc.description.abstract | CCCH-type zinc-finger antiviral protein (ZAP) is a host factor that restricts the infection of many viruses mainly through RNA degradation, translation inhibition and innate immune responses. So far, only one flavivirus, yellow fever virus, has been reported to be ZAP-resistant. Here, we investigated the antiviral potential of human ZAP (isoform ZAP-L and ZAP-S) against three flaviviruses, Japanese encephalitis virus (JEV), dengue virus (DENV) and Zika virus (ZIKV). Infection of JEV but not DENV or ZIKV was blocked by ZAP overexpression, and depletion of endogenous ZAP enhanced JEV replication. ZAP hampered JEV translation and targeted viral RNA for 3'-5' RNA exosome-mediated degradation. The zinc-finger motifs of ZAP were essential for RNA targeting and anti-JEV activity. JEV 3'-UTR, especially in the region with dumbbell structures and high frequencies of CG dinucleotide, was mapped to bind ZAP and confer sensitivity to ZAP. In summary, we identified JEV as the first ZAP-sensitive flavivirus. ZAP may act as an intrinsic antiviral factor through specific RNA binding to fight against JEV infection. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T04:30:56Z (GMT). No. of bitstreams: 1 ntu-107-D01445007-1.pdf: 6004609 bytes, checksum: 3e736e0e3bff9bfa8547549cdd017d74 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員審定書
致謝 中文摘要 I ABSTRACT II TABLE OF CONTENTS III LIST OF FIGURES V LIST OF TABLES VIII CHAPTER 1. INTRODUCTION 1 CHAPTER 2. MATERIALS AND METHODS 6 VIRUSES 6 CELL LINES AND CHEMICALS 6 PLASMID CONSTRUCTS 7 PREPARATION OF LENTIVIRAL VECTORS 9 WESTERN BLOT AND ANTIBODIES 10 REVERSE TRANSCRIPTION, RT-PCR AND REAL-TIME QUANTITATIVE PCR (RT-QPCR) 11 IMMUNOFLUORESCENCE ANALYSIS 11 RNA IMMUNOPRECIPITATION (RIP) ASSAY 12 IN VITRO TRANSCRIPTION 13 MEASUREMENT OF REPLICATION-DEFECTIVE REPLICON RNA STABILITY 14 RNA-BASED REPORTER ASSAY 14 IN VITRO RNA PULL-DOWN ASSAY 14 CROSS-LINKED IMMUNOPRECIPITATION FOLLOWED BY NEXT GENERATION SEQUENCING CLIP-SEQ) 15 STATISTICAL ANALYSIS 17 CHAPTER 3. RESULTS 18 CHAPTER 4. DISCUSSION 27 CHAPTER 5. REFERENCES 31 FIGURES 38 TABLES 62 APPENDIX 65 | |
| dc.language.iso | en | |
| dc.subject | 日本腦炎病毒 | zh_TW |
| dc.subject | 鋅指抗病毒蛋白質 | zh_TW |
| dc.subject | 黃質病毒 | zh_TW |
| dc.subject | 抗病毒機制 | zh_TW |
| dc.subject | Japanese encephalitis virus | en |
| dc.subject | zinc-finger antiviral protein | en |
| dc.subject | antiviral mechanism | en |
| dc.subject | flavivirus | en |
| dc.title | 探討宿主鋅指抗病毒蛋白質抑制黃質病毒感染之機制 | zh_TW |
| dc.title | The antiviral potential and mechanisms of host zinc-finger antiviral protein against flavivirus infection | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳美如,張雯,施嘉和,施信如 | |
| dc.subject.keyword | 鋅指抗病毒蛋白質,日本腦炎病毒,黃質病毒,抗病毒機制, | zh_TW |
| dc.subject.keyword | zinc-finger antiviral protein,Japanese encephalitis virus,flavivirus,antiviral mechanism, | en |
| dc.relation.page | 67 | |
| dc.identifier.doi | 10.6342/NTU201803003 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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