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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 伍安怡 | |
| dc.contributor.author | Ka Wan Cheang | en |
| dc.contributor.author | 鄭家穩 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:30:23Z | - |
| dc.date.available | 2023-09-04 | |
| dc.date.copyright | 2018-09-04 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-16 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72233 | - |
| dc.description.abstract | 登革熱（DF）是一種由登革病毒所引起的急性傳染病，主要經由埃及斑蚊傳播，而具有登革出血熱(DHF)或登革休克症候群(DSS)的患者相對於登革熱(DF)患者有較高的死亡率。已有報導指出蟲媒病毒會利用蟲媒的唾液蛋白其免疫調節的特性，以提高對宿主的感染力。至於蚊子唾液以及其中的蛋白如何調節登革病毒感染宿主依然存在很多的未知。在此研究中我們發現被登革病毒感染的蚊子之唾液會促使巨噬細胞產生TNF。此外，皮內注射Stat1剔除小鼠實驗的結果指出被登革病毒感染的蚊子之唾液較未被病毒感染的蚊子之唾液會導致更顯著的出血反應，並與發炎反應的嚴重程度相關。病毒斑測試結果顯示，皮內注射登革病毒感染的蚊子之唾液的小鼠，在感染後六天可檢測出病毒血症。另外，蚊子感染登革病毒時SRPN23唾液蛋白的表現量會明顯上升，而且SRPN23也會幫助登革病毒在蚊子體內進行複製，從SRPN23靜默之蚊子感染登革病毒後七天所收集的唾液，並經過紫外線進行病毒滅活後，混合登革病毒施打Stat1剔除小鼠，相比施打登革病毒混合滅活的靜默對照組之病毒感染之蚊子唾液，在感染後三天的小鼠血清中能測到顯著較低的病毒量，同時在小鼠的腹部皮膚可測到相對較低的TNF表現量。這個研究顯示蚊子唾液與登革病毒感染宿主所產生的登革出血之嚴重程度相關，而SRPN23是其中一個調節TNF表現量和影響病毒進入血流的唾液蛋白。 | zh_TW |
| dc.description.abstract | Dengue virus (DENV) is transmitted to humans by Aedes aegypti mosquitoes. Arboviruses are known to take advantage of the immunomodulatory properties of mosquito salivary proteins in order to enhance their infectivity in the vertebrate hosts. However, the mechanism of how DENV infection of the mammalian host is regulated by mosquito saliva and its component(s) remains poorly understood. In this study, we discovered that saliva from DENV-infected mosquito stimulated macrophage responses by enhancing DENV-induced TNF production. Moreover, saliva from DENV-infected mosquitos induced more severe hemorrhage and inflammation in Stat1-/- mice than DENV mixed with naïve saliva. Plaque assay results showed that Stat1-/- mice inoculated with saliva from DENV-infected mosquitos had viremia on day 6 after infection whereas mice infected with DENV obtained from culture or mice infected with DENV mixed with saliva from naïve mosquitos did not. Furthermore, we discovered that the expression of mosquito salivary factor SRPN23, a serine protease inhibitor, in salivary gland was regulated by DENV infection. Interestingly, silencing SRPN23 reduced DENV replication in the mosquito. While mice given DENV mixed with saliva from UV-inactivated LacZ-silenced mosquitos had higher viral titer in the serum than mice given DENV alone on day 3, silencing SRPN23 reversed the effect. Furthermore, mice given DENV mixed with saliva from UV-inactivated SRPN23-silenced mosquitos had lower Tnf mRNA expression in the abdominal skin compared to those receiving saliva from UV-inactivated LacZ-silenced mosquitos. This study revealed that mosquito saliva increases hemorrhage severity during DENV infection in the mammalian host and showed that potentially salivary factor SRPN23 is involved in the regulation of Tnf mRNA and viral spread into the bloodstream. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:30:23Z (GMT). No. of bitstreams: 1 ntu-107-R05449014-1.pdf: 4867256 bytes, checksum: 4e75499da86113480bc3c7df78a2feb7 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Table of contents v List of figures viii Chapter I. Introduction 1 1 Dengue virus and disease 1 2 Transmission of dengue virus 2 3 Dengue in Taiwan 3 4 Vector salivary components and those effects during infection 4 5 Dengue hemorrhage mouse model 8 Chapter II. Specific aims 10 Chapter III. Materials and methods 12 1 Materials 12 2 Methods 21 Chapter IV. Results 31 1 Mosquito saliva modulates DENV-induced macrophage cytokine responses 32 2 Saliva from DENV-infected mosquito induces more severe hemorrhage in Stat1-/- mice compared to DENV from C6/36 cell cultures mixed with naïve saliva. 32 3 Mosquito salivary factor induced by DENV infection is critical to DENV replication in Stat1-/- mice. 34 4 Comparison of cytokine and chemokine profiles in the skin of Stat1-/- mice infected with DENV with and without mosquito saliva. 34 5 SRPN23 expression in mosquito tissues and its regulation by blood-feeding and DENV infection 35 6 Silencing SRPN23 A. aegypti inhibits DENV replication in mosquitos 37 7 SRPN23 salivary factor induces viremia in Stat1-/- mice during DENV infection 38 8 The cytokines and chemokines in the skin of Stat1-/- mice are modulated by SRPN23 salivary factor 38 9 SRPN23 salivary factor induces Tnf transcript in DENV-infected Stat1-/- mouse skin 39 Chapter V. Discussion 41 1 Stat1-/- mice and dengue hemorrhage mouse model 41 2 How does DENV-induced mosquito salivary factor(s) enhance hemorrhage development? 42 3 How does SRPN23 affect DENV infection in stat1-/- mice? 43 4 Conclusions 45 Chapter VI. References 46 Chapter VII. Figures 56 | |
| dc.language.iso | en | |
| dc.subject | 埃及斑蚊 | zh_TW |
| dc.subject | 登革病毒 | zh_TW |
| dc.subject | 唾液 | zh_TW |
| dc.subject | 出血 | zh_TW |
| dc.subject | DENV | en |
| dc.subject | Aedes aegypti | en |
| dc.subject | saliva | en |
| dc.subject | hemorrhage | en |
| dc.title | 探討在登革病毒感染下埃及斑蚊之唾液/SRPN23唾液蛋白對免疫反應與出血反應所造成的影響 | zh_TW |
| dc.title | The effect of Aedes aegypti saliva/SRPN23 salivary protein on immune response and hemorrhage development in DENV infection | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 顧家綺,蕭信宏 | |
| dc.subject.keyword | 登革病毒,埃及斑蚊,唾液,出血, | zh_TW |
| dc.subject.keyword | DENV,Aedes aegypti,saliva,hemorrhage, | en |
| dc.relation.page | 96 | |
| dc.identifier.doi | 10.6342/NTU201803692 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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