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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蕭信宏(Shin-Hong Shiao) | |
| dc.contributor.author | Hui-Zhen Xu | en |
| dc.contributor.author | 徐慧真 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:49:52Z | - |
| dc.date.copyright | 2020-09-01 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-17 | |
| dc.identifier.citation | Bale. (2012). Emerging viral infections. Seminars in Pediatric Neurology, 19(3), 152-157. Bhatt, Gething, Brady, et al. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504-507. Broutet, Krauer, Riesen, et al. (2016). Zika Virus as a Cause of Neurologic Disorders. New England Journal of Medicine, 374(16), 1506-1509. Chambers, Weir, Grakoui, et al. (1990). Evidence that the N-terminal domain of nonstructural protein NS3 from yellow fever virus is a serine protease responsible for site-specific cleavages in the viral polyprotein. Proceedings of the National Academy of Sciences of the United States of America, 87(22), 8898-8902. Chavez-Salinas, Ceballos-Olvera, Reyes-Del Valle, et al. (2008). Heat shock effect upon dengue virus replication into U937 cells. Virus Research, 138(1-2), 111-118. Christophers. (1960). Aëdes aegypti (L.) the Yellow Fever Mosquito: its Life History, Bionomics and Structure. New York: Cambridge University Press Collins, Barrett. (2017). Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day. Current Infectious Disease Reports, 19(3), 14. Cowman, Berry, Baum. (2012). The cellular and molecular basis for malaria parasite invasion of the human red blood cell. Journal of Cell Biology, 198(6), 961-971. Cowman, Berry, Baum. (2012). The cellular and molecular basis for malaria parasite invasion of the human red blood cell. Journal of Cell Biology, 198(6), 961-971. Center for Disease Control and Prevention. (2020). Yellow Fever Vaccine. https://www.cdc.gov/yellowfever/vaccine/index.html Center for Disease Control and Prevention. (2020). Yellow Book Chapter 4 Travel-Related Infectious Diseases - Chikungunya. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/chikungunya Center for Disease Control and Prevention. (2020). Yellow Book Chapter 4 Travel- Related Infectious Diseases- Japanese encephalitis. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/japanese-encephalitis Center for Disease Control and Prevention. (2020). West Nile virus - Symptoms, Diagnosis, Treatment https://www.cdc.gov/westnile/symptoms/index.html Center for Disease Control and Prevention. (2019). Parasite – Lymphatic Filarisis - Epidemiology Risk Factors. https://www.cdc.gov/parasites/lymphaticfilariasis/epi.html Center for Disease Control and Prevention. (2019). Zika virus – Treament. https://www.cdc.gov/zika/symptoms/treatment.html Center for Disease Control and Prevention. (2019). Travelers’ Health - Zika Travel Information. https://wwwnc.cdc.gov/travel/page/zika-information Dai, Whitesell, Rogers, et al. (2007). Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell, 130(6), 1005-1018. De Alwis, Williams, Schmid, et al. (2014). Dengue viruses are enhanced by distinct populations of serotype cross-reactive antibodies in human immune sera. Public Library of Science Pathogens, 10(10), e1004386. Goldberg. (2013). Complex nature of malaria parasite hemoglobin degradation. Proceedings of the National Academy of Sciences, 110(14), 5283-5284. Guy, Briand, Lang, et al. (2015). Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward. Vaccine, 33(50), 7100-7111. Guzman, Alvarez, Halstead. (2013). Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Archives of Virology, 158(7), 1445-1459. Guzman, Gubler, Izquierdo, et al. (2016). Dengue infection. Nature Review Disease Primers, 2, 16055. Hadinegoro, Arredondo-García, Capeding, et al. (2015). Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. New England Journal of Medicine, 373(13), 1195-1206. Halstead. (2008). Dengue virus-mosquito interactions. Annual Review Entomology, 53, 273-291. Halstead, Thomas. (2011). New Japanese encephalitis vaccines: alternatives to production in mouse brain. Expert Review of Vaccines, 10(3), 355-364. Hamel, Dejarnac, Wichit, et al. (2015). Biology of Zika Virus Infection in Human Skin Cells. Journal of Virology, 89(17), 8880-8896. Hendrick, Hartl. (1993). MOLECULAR CHAPERONE FUNCTIONS OF HEAT-SHOCK PROTEINS. Annual Review of Biochemistry, 62(1), 349-384. Jain, Coloma, García-Sastre, et al. (2016). Structure of the NS3 helicase from Zika virus. Nature structural molecular biology, 23(8), 752-754. Kijima, Prince, Tigue, et al. (2018). HSP90 inhibitors disrupt a transient HSP90-HSF1 interaction and identify a noncanonical model of HSP90-mediated HSF1 regulation. Scientific Reports, 8(1), 6976. Kindhauser, Allen, Frank, et al. (2016). Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ, 94(9), 675-686c. Klase, Khakhina, Schneider, et al. (2016). Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. Public Library of Science Neglected Tropical Diseases, 10(8), e0004877. Kumar, Liang, Aarthy, et al. (2018). Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease. American Chemical Society omega, 3(12), 18132-18141. Linthicum, Britch, Anyamba. (2016). Rift Valley Fever: An Emerging Mosquito-Borne Disease. Annual Review of Entomology, 61(1), 395-415. Mendillo, Santagata, Koeva, et al. (2012). HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers. Cell, 150(3), 549-562. Ming, Tang, Song. (2016). Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities. Cell Stem Cell, 19(6), 690-702. Mukhopadhyay, Kuhn, Rossmann. (2005). A structural perspective of the flavivirus life cycle. Nature Reviews Microbiology, 3(1), 13-22. Neckers, Blagg, Haystead, et al. (2018). Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development. Cell Stress Chaperones, 23(4), 467-482. Pearl. (2016). Review: The HSP90 molecular chaperone-an enigmatic ATPase. Biopolymers, 105(8), 594-607. Petersen, Jamieson, Powers, et al. (2016). Zika Virus. New England Journal of Medicine, 374(16), 1552-1563. Quel, Pinheiro, Rodrigues, et al. (2020). Heat shock protein 90 kDa (Hsp90) from Aedes aegypti has an open conformation and is expressed under heat stress. International Journal of Biological Macromolecules, 156, 522-530. Rosenzweig, Nillegoda, Mayer, et al. (2019). The Hsp70 chaperone network. Nature Reviews Molecular Cell Biology, 20(11), 665-680. Salazar, Richardson, Sánchez-Vargas, et al. (2007). Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. Biomedcentral Microbiology, 7(1), 9. Screaton, Mongkolsapaya, Yacoub, et al. (2015). New insights into the immunopathology and control of dengue virus infection. Nature Reviews Immunology, 15(12), 745-759. Shang, Wu, Huang, et al. (2020). Inhibition of heat shock protein 90 suppresses Bombyx mori nucleopolyhedrovirus replication in B. mori. Insect Molecular Biology, 29(2), 205-213. Sreedhar, Soti, Csermely. (2004). Inhibition of Hsp90: a new strategy for inhibiting protein kinases. Biochimica et Biophysica Acta, 1697(1-2), 233-242. Srisutthisamphan, Jirakanwisal, Ramphan, et al. (2018). Hsp90 interacts with multiple dengue virus 2 proteins. Scientific Reports, 8(1), 4308. Stadler, Allison, Schalich, et al. (1997). Proteolytic activation of tick-borne encephalitis virus by furin. Journal of Virology, 71(11), 8475-8481. Taguwa, Yeh, Rainbolt, et al. (2019). Zika Virus Dependence on Host Hsp70 Provides a Protective Strategy against Infection and Disease. Cell reports, 26(4), 906-920.e903. Tjaden, Thomas, Fischer, et al. (2013). Extrinsic Incubation Period of Dengue: Knowledge, Backlog, and Applications of Temperature Dependence. Public Library of Science Neglected Tropical Diseases, 7(6), e2207. Ujino, Yamaguchi, Shimotohno, et al. (2009). Heat-shock protein 90 is essential for stabilization of the hepatitis C virus nonstructural protein NS3. The Journal of Biological Chemistry, 284(11), 6841-6846. Verma, Goyal, Jamal, et al. (2016). Hsp90: Friends, clients and natural foes. Biochimie, 127, 227-240. Vihervaara, Sistonen. (2014). HSF1 at a glance. Journal of Cell Science, 127(2), 261-266. Vu, Nguyen, Tran, et al. (2018). Immunogenicity and safety of a single dose of a live attenuated Japanese encephalitis chimeric virus vaccine in Vietnam: A single-arm, single-center study. International Journal of Infectious Disease, 66, 137-142. Weaver, Lecuit. (2015). Chikungunya virus and the global spread of a mosquito-borne disease. New England Journal of Medicine, 372(13), 1231-1239. World Health Organization. (2017). Global vector control response 2017–2030. https://www.who.int/publications/i/item/9789241512978 World Health Organization. (2017). World malaria report 2019. https://www.afro.who.int/publications/world-malaria-report-2019 World Health Organization. (2020). Dengue and severe dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue Yu, Zhang, Holdaway, et al. (2008). Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation. Science, 319(5871), 1834-1837. Zeldenryk, Gordon, Gray, et al. (2012). Disability measurement for lymphatic filariasis: a review of generic tools used within morbidity management programs. Public Library of Science Neglected Tropical Diseases, 6(9), e1768. Zhang, Ge, Yu, et al. (2013). Cryo-EM structure of the mature dengue virus at 3.5-Å resolution. Nature structural molecular biology, 20(1), 105-110. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15676 | - |
| dc.description.abstract | 蚊子是許多傳染病的主要病媒，舉凡瘧疾、絲蟲病、日本腦炎、登革熱、屈躬病，乃至近年爆發的茲卡病毒感染症 (Zika virus infection)，皆是經由不同種類的病媒蚊感染人類。目前茲卡病毒的防治多利用噴灑殺蟲劑控制病媒蚊數量作為主要降低病毒傳播的方式，並無有效之疫苗及藥物可供預防及治療。而針對突變率較高之RNA病毒設計藥物也易有抗藥性的產生，因此積極開發新穎替代性策略是首要之務。過去的文獻指出，茲卡病毒的非結構性蛋白 (nonstructural proteins, NSs) 會參與病毒自身的複製與組裝，並透過活化螺旋酶 (helicase) 與蛋白酶 (protease) 進行病毒蛋白的修飾。而在哺乳動物及昆蟲的模式研究中，宿主細胞的熱休克蛋白90 (Heat shock protein 90, Hsp90) 不僅會與茲卡病毒NS3蛋白有交互作用，當Hsp90被降解，也會使病毒複製能力下降。因此本研究將利用埃及斑蚊為研究模式，探討病媒蚊體內Hsp90與茲卡病毒NS3作為抑制病毒複製標的蛋白的可能性。從初步的實驗結果中，我們發現Hsp90與NS3不僅有形成複合物的現象，且Hsp90的表現受到抑制時，也會影響茲卡病毒的感染率。此外我們利用病毒蛋白抑制劑 (Hydroxychloroquine) 抑制NS3被後會影響Hsp90蛋白的表現。因此，我們推測茲卡病毒可能透過NS3蛋白切割的方式，改變宿主體內Hsp90表現，藉此進行調控病毒複製與增殖的能力。我們預期透過抑制Hsp90能干擾NS3發揮正常功能，因此降低病毒數量及感染率。未來我們也會經由調控Hsp90的表現，更進一步去了解茲卡病毒與埃及斑蚊體內蛋白間調控的分子機制，期許能為研發抗病毒藥物提供一個可能的方向。 | zh_TW |
| dc.description.abstract | The mosquito is the main vector of several important arthropod-borne diseases, such as malaria, filariasis, Japanese encephalitis, dengue fever, chikungunya and Zika. These diseases are transmitted from human to human by different mosquito vectors. However, no effective vaccine and medication are available for Zika virus infection until now. Currently, vector control through insecticide treatment become the main approach to reduce the transmission of Zika virus. However, the fast modification on RNA viral genome might neutralize the effect of inhibition. Therefore, development of alternative strategies for mosquito-borne disease control is urgently required. Previous reports indicated that ZIKV nonstructural proteins (NSs) participated in the viral replication and protein assembly, whereas the viral protein processing was mediated by non-structure protein 3 (NS3) through helicase and protease activity. In addition, NS3 has been shown to interact with heat shock protein 90 (Hsp90) in mammalian model. When hsp90 be silenced in insect cell, the virus replication be suppressed. Our preliminary results showed that Hsp90 interacted with NS3, and viral infectivity was reduced by inhibition of Hsp90 through reverse genetic approach. We also showed that inhibition of NS3 by hydroxychloroquine resulted in the inhibition of Hsp90 expression. We hypothesize that NS3 might play important role of modulating Hsp90 function through its protease activity. In the future, we will further investigate the detail mechanism underlying the regulation between ZIKV protein and host heat shock proteins. Information gathered in this study will pave the way toward the drug development by using molecular engineering approaches. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T17:49:52Z (GMT). No. of bitstreams: 1 U0001-0308202015242300.pdf: 4158774 bytes, checksum: 63935bca9156c25ade60c37173ba32b8 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 i 摘要 ii Abstract iii 目錄 iv 圖目錄 viii 表目錄 ix 第一章 緒論 1 1.1. 病媒蚊傳播疾病 (Mosquito-borne disease) 1 1.1.1. 台灣的蚊媒疾病 (Mosquito-borne disease in Taiwan) 3 1.1.1.1. 瘧疾 (Malaria) 3 1.1.1.2. 登革熱 (Dengue fever) 3 1.2. 埃及斑蚊生活史 (The life cycle of Aedes aegypti) 4 1.3. 茲卡病毒感染症 (Zika virus infection) 5 1.3.1. 臨床症狀 5 1.3.2. 國際之流行病學 5 1.3.3. 茲卡病毒生活史 6 1.3.3.1. 宿主細胞細胞內之複製 6 1.3.3.2. 病媒蚊體內之複製 6 1.4. 非結構性蛋白 (Non-structural protein 3，NS3) 參與病毒蛋白之成熟 7 1.5. 熱休克蛋白 (Heat shock proteins) 8 1.5.1. 熱休克蛋白家族 (Heat shock protein family) 8 1.5.1.1. 熱休克蛋白90 (Heat shock protein 90) 8 1.5.1.2. 熱休克蛋白70 (Heat shock protein 70) 9 1.5.1.3. 熱休克轉錄因子 1 (Heat shock transcription factor 1, HSF1) 9 1.6. 實驗動機 10 第二章 實驗材料與方法 11 2.1. 實驗步驟與流程 11 2.1.1. 埃及斑蚊之飼養與繼代 11 2.1.2. 病毒培養 (Virus culture) 12 2.1.3. 埃及斑蚊之餵血 12 2.1.4. 雙股RNA (double-stranded RNA, dsRNA) 製備 12 2.1.4.1. 質體建構 (plasmid construction) 12 2.1.4.2. 雙股RNA合成 (dsRNA synthesis) 13 2.1.5. RNA萃取 (RNA extraction) 14 2.1.6. 反轉錄作用 (reverse transcription, RT) 14 2.1.7. 聚合酶連鎖反應 (polymerase chain reaction, PCR) 15 2.1.8. 即時定量聚合酶連鎖反應 (real-time PCR, Quantitative PCR, q-PCR) 15 2.1.9. 埃及斑蚊胸部注射 (Injection) 15 2.1.9.1. 病毒注射 (Virus injection) 15 2.1.10. RNAi-mediated silencing 與 knock-down efficiency test 16 2.1.11. 西方點墨法 (Western blot analysis ) 16 2.1.12. Hsp90 抑制試驗 (Hsp90 inhibiton assay) 17 2.1.13. 細胞培養 (Cell culture) 17 2.1.14. 溶斑試驗 (Plaque assay) 18 2.1.15. 免疫螢光染色法 (Immunofluorescence assay, IFA) 18 2.1.15.1. 組織免疫螢光染色法 18 2.1.15.2. 細胞免疫螢光染色法 19 2.1.16. 免疫沉澱試驗 (Immunoprecipitation , IP) 20 2.1.17. NS3抑制試驗 (NS3 inhibiton assay) 20 2.1.18. 細胞轉染 (Transfection) 21 2.2. 實驗試劑之配置 22 第三章 結果 24 3.1. 確認埃及斑蚊與人類之Hsp90蛋白序列相似性 24 3.2. 埃及斑蚊吸血方式感染ZIKV後Hsp90之表現情形 24 3.3. RNAi抑制Hsp90之效率以及對ZIKV表現量之影響 25 3.4. 抑制Hsp90對於ZIKV之感染力影響 26 3.5. ZIKV與Hsp90於Midgut、Salivary gland中位置相關性 27 3.6. 探討ZIKV病毒蛋白與埃及斑蚊Hsp90蛋白間之交互作用 28 3.7. 抑制Hsp90對於ZIKV之NS3於Midgut、Salivary gland中表現 28 3.8. 以Hsp90 inhibitor抑制Hsp90對於ZIKV成熟過程中的影響 29 3.9. 以NS3 inhibitor抑制ZIKV病毒蛋白表現對於Hsp90之影響 29 3.10. 設計Hsp90 HA-tag 的Overexpression系統觀察Hsp90對NS3之影響 30 第四章 討論 31 4.1. 埃及斑蚊與人類Hsp90之相似性 31 4.2. 埃及斑蚊Hsp90之表現情形及表現位置 31 4.3. 埃及斑蚊Hsp90對ZIKV之影響 32 4.4. Hsp90在埃及斑蚊被ZIKV感染後參與病毒複製的過程 33 附圖 35 附表 65 參考文獻 69 | |
| dc.language.iso | zh-TW | |
| dc.subject | 蟲媒疾病 | zh_TW |
| dc.subject | 茲卡病毒 | zh_TW |
| dc.subject | 熱休克蛋白90 | zh_TW |
| dc.subject | 非結構性蛋白3 | zh_TW |
| dc.subject | 埃及斑蚊 | zh_TW |
| dc.subject | Aedes aegypti | en |
| dc.subject | arthropod-borne diseases | en |
| dc.subject | Hsp90 | en |
| dc.subject | NS3 | en |
| dc.subject | zika virus | en |
| dc.title | 埃及斑蚊熱休克蛋白90與茲卡病毒非結構性蛋白NS3之交互關係研究 | zh_TW |
| dc.title | Study of the Zika virus NS3 protein and Hsp90 interaction on virus replication in the mosquito Aedes aegypti | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 洪健清(Chien-Ching Hung) | |
| dc.contributor.oralexamcommittee | 顧家綺(Chia-Chi Ku),張永祺(Yung-Chiy Chang) | |
| dc.subject.keyword | 茲卡病毒,埃及斑蚊,非結構性蛋白3,熱休克蛋白90,蟲媒疾病, | zh_TW |
| dc.subject.keyword | Aedes aegypti,zika virus,NS3,Hsp90,arthropod-borne diseases, | en |
| dc.relation.page | 75 | |
| dc.identifier.doi | 10.6342/NTU202002280 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-18 | |
| 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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