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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 吳金洌(Jen-Leih Wu) | |
dc.contributor.author | Hsu-Yu Chen | en |
dc.contributor.author | 陳叙伃 | zh_TW |
dc.date.accessioned | 2021-06-08T05:09:56Z | - |
dc.date.copyright | 2011-07-26 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-19 | |
dc.identifier.citation | 1. Haller O, Kochs G, Weber F (2007) Interferon, Mx, and viral countermeasures. Cytokine Growth Factor Rev 18: 425-433.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23774 | - |
dc.description.abstract | 第一型干擾素(Type I interferon)在先天免疫反應中扮演重要角色。其功能為在細胞受感染時能活化下游抗病毒蛋白,以抑制病毒之感染及複製。模式辨識受體(PAMPs receptors) 可偵測外來病原之特定核酸、蛋白或其它結構而啟動誘發IFN之訊息傳遞,被認為是先天免疫系統中之第一道防線。目前已知可辨識RNA病毒之PAMPs receptors包含: TLR3、TLR7、TLR22、MDA5及RIG-I。神經壞死病毒(nervous necrosis virus),為不含套模之RNA 病毒,主要感染魚類中樞神經系統,主要之天然宿主為重要之經濟物種石斑魚,近年來其感染造成台灣石斑養殖漁業重大損失。過去研究中以斑馬魚作為模式生物之研究發現,干擾素在 NNV致病機轉中扮演重要角色。實驗中,NNV 感染能誘發IFN 及下游抗病毒蛋白(Mx, p-eIF2α)之活化表現。然而,同樣抗免疫基因在感染之斑馬魚幼體中卻無法以RT-PCR偵測出,且感染造成幼魚高達90% 之死亡率。研究結果指出,IFN 之活化在對抗NNV 之感染中扮演關鍵性角色。然而,NNV 感染中之IFN 活化途徑及機制目前尚未清楚研究,因此,本研究之目的為: (1)探討NNV感染中IFN 之誘發機制。(2)此誘發路徑在斑馬魚不同發育階段之表現量差異。以分子機制之角度深入了解NNV之致病機轉及其在魚類發育早期所造成嚴重病變死亡之原因。
實驗中以斑馬魚之胚胎細胞株ZF-4做為感染模式,在細胞實驗中分析參與NNV 感染中IFN活化之模式辨識受體。實驗發現,位於細胞質中之模式辨識受體RIG-I可能在IFN的活化中扮演主要的角色。進一步研究中以反義核酸抑制細胞中RIG-I 基因表現,以證實其對啟動免疫反應之重要性。結果發現,RIG-I抑制後,細胞感染所誘發之IFN表現低於正常表現RIG-I之細胞約50倍。在RIG-I發育階段表現量之實驗中,亦初步證實成魚之基因表現量高於發育早期之幼魚約五倍。研究結果顯示RIG-I在NNV感染中為主要辨識病毒並活化免疫反應之模式辨識受體。 | zh_TW |
dc.description.abstract | Type I Interferon (IFN), an important group of cytokine, can induce an antiviral state in most nucleated cells. In previous studies, we used zebrafish as a pathogenesis model and found that IFN response was involved in NNV infection. Nervous necrosis virus (NNV), a non-envelope virus which has bipartite genomes composed of two positive-sense RNAs, is a major fish pathogen that causes enormous loss for the aquaculture industry. NNV is known that it can causes acute infection and leads to high mortality in larvae, while causes persistent infection and leads to lower mortality in adult. Our previous research shows that the IFN system had been induced after infection in adult. However, IFN response in NNV infected larva was fail to be activated. Moreover, IFN pre-treatment in larva can rescue the mortality caused by NNV. This indicated that IFN induction plays a key role in protecting infected larvae. Several Pathogen associated molecular Patterns (PAMPs) receptors have been reported that can recognize virus RNA and trigger the IFN response. Our results show that cytosolic receptor RIG-I was highly activated after infection. Furthermore, its expression pattern was fit with the IFN induction. The knockdown experiments confirm the major role played by RIG-I in IFN induction upon NNV infection. At last, the RIG-I signaling in wild type larvae was much lower compare to the adult. Considering these result, we propose that IFN was mainly trigger by RIG-I signaling in NNV infection, and the insufficient expression of RIG-I causes weak IFN response and acute infection in larval fish. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:09:56Z (GMT). No. of bitstreams: 1 ntu-100-R98b45028-1.pdf: 3641055 bytes, checksum: 42ce43213545aec352e6a53bcef43046 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 1. Interferon and antivirus defense 4
2. Transcriptional activation of type I IFN genes 6 3. Nervous necrosis virus 9 4. The specific aim: to clarify the PRRs involved in type I interferon response upon nervous necrosis virus infection 10 2 Materials and methods 13 1. Cell lines 13 2. Infection and poly I:C transfection 13 3. Morpholino knockdown 14 4. Fish 15 5. Total RNA extraction 15 6. Real-time RT PCR 15 7. Semi-quantitative RT-PCR 16 8. Statistic analysis 17 3 Results 18 1. The susceptibility of ZF-4 cells to NNV infection 18 2. The expression of IFNΦ1 increased after NNV infection 18 3. The expression of two PRRs: RIG-I and MDA5 increased after NNV infection 19 4. Morpholino delivery in ZF-4 cells 20 5. RIG-I knockdown repressed the IFN induction and enhanced cell mortality upon NNV infection 22 6. The RIG-I dependent signaling expression pattern at different developmental stages in zebrafish 24 4 Discussions 26 1. The PRRs involve in IFN response during NNV infection 26 2. RIG-I mediated signaling play a major role in IFN induction during NNV infection 28 3. NNV release RNA genomes from particles after escape from endocytosis vesicles and entry into cytoplasm 29 4. The recognition and binding of RIG-I to NNV RNAs 30 5. The stage-specific expression pattern of RIG-I mediated signaling 31 5 Reference 33 6 Figures 38 Figure 1. CPE development in different MOI of NNV infected ZF-4 cells. 38 Figure 2. NNV RNA2 replication in ZF-4 cells infected with different MOI. 39 Figure 3. IFNΦ1 induction in ZF-4 cells infected with different titers of virus. 40 Figure 4. IFNΦ1 induction in ZF-4 cells infected with 104 TCID50 of NNV 41 Figure 5. RIG-I expression in ZF-4 cells after NNV infection 42 Figure 6. MDA5 expression in ZF-4 cells after NNV infection 43 Figure 7. TLR3 expression in ZF-4 cells after NNV infection. 44 Figure 8. TLR7expression in ZF-4 cells after NNV infection. 45 Figure 9. TLR22 expression in ZF-4 cells after NNV infection 46 Figure 10. Endo-porter delivery of 5mis RIG-I MOs (3’ Fluorescein) 47 Figure 11. PolyJet delivery of 5mis RIG-I MOs (3’ Fluorescein) 48 Figure 12. GenMute delivery of 5mis RIG-I MOs (3’ Fluorescein) 49 Figure 13. PepMute delivery of 5mis RIG-I MOs(3’ Fluorescein) 50 Figure 14. RIG-I MOs-induced alternative splicing resulting in deletion of exon 2. 51 Figure 15. RIG-I induction in RIG-I knockdown cells infected with NNV 52 Figure 16. IFNΦ1 induction in RIG-I knockdown cells infected with NNV 53 Figure 17. RIG-I knockdown enhanced CPE and cell mortality in NNV infection. 54 Figure 18. The involvement of RIG-I dependent/independent pathway in IFN response during NNV infection 55 7 Table 56 Table 1. Primers for qPCR and semi-RT PCR 56 8 Appendix 57 1. GenMute delivery system (SignaGen Laboratories) 57 | |
dc.language.iso | en | |
dc.title | 模式辨識受體RIG-I 於神經壞死病毒感染中第一型干擾素之誘發角色 | zh_TW |
dc.title | The retinoic acid-inducible gene I plays a major role in interferon induction during NNV infection | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 邱品文(Pin-Wen Chiou),洪健睿(Jiann-Ruey Hong),呂明偉(Ming-Wei Lu),陳志毅(Jyh-Yih Chen) | |
dc.subject.keyword | 神經壞死病毒,先天免疫反應,干擾素,模式辨識受體,斑馬魚, | zh_TW |
dc.subject.keyword | nervous necrosis virus,innate immune response,interferon,Pathogen associated molecular Patterns receptors,zebrafish,Retinoic acid-inducible gene I, | en |
dc.relation.page | 57 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-07-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 漁業科學研究所 | zh_TW |
顯示於系所單位: | 漁業科學研究所 |
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