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  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50012
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor翁啟惠(Chi-Huey Wong)
dc.contributor.authorYen-Lung Loen
dc.contributor.author駱衍龍zh_TW
dc.date.accessioned2021-06-15T12:27:45Z-
dc.date.available2017-08-24
dc.date.copyright2016-08-24
dc.date.issued2016
dc.date.submitted2016-08-09
dc.identifier.citation1. World Health Organization. Global strategy for dengue prevention and control 2012-2020 (in IRIS). Geneva: World Health Organization; 2012. v, 35 p. p.
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4. van der Schaar HM, Rust MJ, Waarts BL, van der Ende-Metselaar H, Kuhn RJ, Wilschut J, et al. Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J Virol. 2007;81(21):12019-28.
5. Miller JL, de Wet BJ, Martinez-Pomares L, Radcliffe CM, Dwek RA, Rudd PM, et al. The mannose receptor mediates dengue virus infection of macrophages. PLoS pathogens. 2008;4(2):e17.
6. Tassaneetrithep B, Burgess TH, Granelli-Piperno A, Trumpfheller C, Finke J, Sun W, et al. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med. 2003;197(7):823-9.
7. Taniguchi N. Glycoscience : biology and medicine. New York: Springer; 2014. pages cm p.
8. Garcia-Vallejo JJ, van Kooyk Y. The physiological role of DC-SIGN: a tale of mice and men. Trends Immunol. 2013;34(10):482-6.
9. Martinez-Pomares L. The mannose receptor. Journal of leukocyte biology. 2012;92(6):1177-86.
10. Green AM, Beatty PR, Hadjilaou A, Harris E. Innate immunity to dengue virus infection and subversion of antiviral responses. J Mol Biol. 2014;426(6):1148-60.
11. Aoki N, Kimura Y, Kimura S, Nagato T, Azumi M, Kobayashi H, et al. Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells. Journal of leukocyte biology. 2009;85(3):508-17.
12. Batliner J, Mancarelli MM, Jenal M, Reddy VA, Fey MF, Torbett BE, et al. CLEC5A (MDL-1) is a novel PU.1 transcriptional target during myeloid differentiation. Molecular immunology. 2011;48(4):714-9.
13. Chen ST, Lin YL, Huang MT, Wu MF, Cheng SC, Lei HY, et al. CLEC5A is critical for dengue-virus-induced lethal disease. Nature. 2008;453(7195):672-6.
14. Chen ST, Liu RS, Wu MF, Lin YL, Chen SY, Tan DT, et al. CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality. PLoS pathogens. 2012;8(4):e1002655.
15. Cheung R, Shen F, Phillips JH, McGeachy MJ, Cua DJ, Heyworth PG, et al. Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice. The Journal of clinical investigation. 2011;121(11):4446-61.
16. Tung YT, Wu MF, Wang GJ, Hsieh SL. Nanostructured electrochemical biosensor for th0065 detection of the weak binding between the dengue virus and the CLEC5A receptor. Nanomedicine : nanotechnology, biology, and medicine. 2014;10(6):1335-41.
17. Watson AA, Lebedev AA, Hall BA, Fenton-May AE, Vagin AA, Dejnirattisai W, et al. Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling. The Journal of biological chemistry. 2011;286(27):24208-18.
18. Watson AA, O'Callaghan CA. Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor. Acta crystallographica Section F, Structural biology and crystallization communications. 2010;66(Pt 1):29-31.
19. Wu MF, Chen ST, Yang AH, Lin WW, Lin YL, Chen NJ, et al. CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages. Blood. 2013;121(1):95-106.
20. Yang YL, Chang WP, Hsu YW, Chen WC, Yu HR, Liang CD, et al. Lack of association between CLEC5A gene single-nucleotide polymorphisms and Kawasaki disease in Taiwanese children. Journal of biomedicine & biotechnology. 2012;2012:398628.
21. Cruz-Oliveira C, Freire JM, Conceicao TM, Higa LM, Castanho MA, Da Poian AT. Receptors and routes of dengue virus entry into the host cells. FEMS Microbiol Rev. 2015;39(2):155-70.
22. Diamond MS, Pierson TC. Molecular Insight into Dengue Virus Pathogenesis and Its Implications for Disease Control. Cell. 2015;162(3):488-92.
23. Horstick O, Tozan Y, Wilder-Smith A. Reviewing dengue: still a neglected tropical disease? PLoS Negl Trop Dis. 2015;9(4):e0003632.
24. Schwartz LM, Halloran ME, Durbin AP, Longini IM, Jr. The dengue vaccine pipeline: Implications for the future of dengue control. Vaccine. 2015;33(29):3293-8.
25. Hsu TL, Cheng SC, Yang WB, Chin SW, Chen BH, Huang MT, et al. Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins. The Journal of biological chemistry. 2009;284(50):34479-89.
26. Lee RT, Hsu TL, Huang SK, Hsieh SL, Wong CH, Lee YC. Survey of immune-related, mannose/fucose-binding C-type lectin receptors reveals widely divergent sugar-binding specificities. Glycobiology. 2011;21(4):512-20.
27. Wang WK, Lee CN, Kao CL, Lin YL, King CC. Quantitative competitive reverse transcription-PCR for quantification of dengue virus RNA. J Clin Microbiol. 2000;38(9):3306-10.
28. Wang WK, Sung TL, Tsai YC, Kao CL, Chang SM, King CC. Detection of dengue virus replication in peripheral blood mononuclear cells from dengue virus type 2-infected patients by a reverse transcription-real-time PCR assay. J Clin Microbiol. 2002;40(12):4472-8.
29. Lagache T, Sauvonnet N, Danglot L, Olivo-Marin JC. Statistical analysis of molecule colocalization in bioimaging. Cytometry A. 2015;87(6):568-79.
30. Cambi A, de Lange F, van Maarseveen NM, Nijhuis M, Joosten B, van Dijk EM, et al. Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells. J Cell Biol. 2004;164(1):145-55.
31. Panyi G, Bagdany M, Bodnar A, Vamosi G, Szentesi G, Jenei A, et al. Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes. Proc Natl Acad Sci U S A. 2003;100(5):2592-7.
32. Vereb G, Matko J, Vamosi G, Ibrahim SM, Magyar E, Varga S, et al. Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. Proc Natl Acad Sci U S A. 2000;97(11):6013-8.
33. Verreck FA, de Boer T, Langenberg DM, Hoeve MA, Kramer M, Vaisberg E, et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci U S A. 2004;101(13):4560-5.
34. Dejnirattisai W, Webb AI, Chan V, Jumnainsong A, Davidson A, Mongkolsapaya J, et al. Lectin switching during dengue virus infection. J Infect Dis. 2011;203(12):1775-83.
35. Pokidysheva E, Zhang Y, Battisti AJ, Bator-Kelly CM, Chipman PR, Xiao C, et al. Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell. 2006;124(3):485-93.
36. van der Schaar HM, Rust MJ, Chen C, van der Ende-Metselaar H, Wilschut J, Zhuang X, et al. Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS pathogens. 2008;4(12):e1000244.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50012-
dc.description.abstract登革熱是一種好發於全球熱帶與亞熱帶的重要病媒蚊傳染性疾病。登革病毒感染人類巨噬細胞時利用人類甘露糖受體與DC-SIGN作為用以穩定附著於巨噬細胞的主要受體,並利用凝集素CLEC5A作為次要附著受體,用以引發先天免疫系統的訊號傳遞以防禦病毒攻擊。但人類甘露糖受體與DC-SIGN這類主要附著受體如何與凝集素CLEC5A這類訊息受體交互作用與協同功能至今仍沒有被探討。本論文提出一個可能的模型,試著解釋具較強附著能力的受體如甘露糖受體與DC-SIGN與較弱附著能力的受體如CLEC5A,透過共同分布於一個夠小的範圍內以足以與登革熱病毒形成多價異元複合體,高附著能力的受體可以吸引登革病毒穩定在其上,而較弱附著能力的訊息受體可以因為分布在高附著能力受體的周邊提高與登革熱病毒的直接接觸的能力,提高引發先天免疫系統的觸發效率,並以此多價異元複合體賦予病毒附著與訊息傳遞間必要的邏輯連結,且提供抗病毒策略的新穎線索。zh_TW
dc.description.abstractDengue fever is a mosquito-borne viral pandemic disease that is widespread in tropical and subtropical areas. Dengue virus uses human mannose-binding receptor (hMR) and DC-SIGN on macrophages as primary receptors, and CLEC5A as signaling receptor to sense the dengue virus invasion and then to signal and stimulate macrophages to secrete cytokines. But the interplay between hMR/DC-SIGN and CLEC5A is unknown. Here we demonstrate a plausible mechanism for the interaction: hMR/DC-SIGN first attracts the virus with high avidity, then interaction with CLEC5A in close proximity forms a multivalent heterocomplex and facilitates CLEC5A-mediated signal transduction. Our study suggests that the cooperation between a high-avidity lectin-virus interaction and a nearby low-avidity signaling receptor provides a necessary connection between binding and signaling. Understanding this mechanism may lead to the development of a new antiviral strategy.en
dc.description.provenanceMade available in DSpace on 2021-06-15T12:27:45Z (GMT). No. of bitstreams: 1
ntu-105-D95b46013-1.pdf: 2767960 bytes, checksum: 7a6cc133cd893b1bcd27da614d9aebdb (MD5)
Previous issue date: 2016
en
dc.description.tableofcontents中文摘要--02
英文摘要--03
Chapter 1. Introduction--04
Chapter 2. Material and Method--08
Chapter 3. Results--13
Chapter 4. Discussion--27
Acknowledgements--38
References--39
Appendix--42
A1: Elucidate CLEC5A/dengue virus binding mode--43
A2: Glycan profile of dengue virus envelop protein--45
A3: Up to 50 Liter scale dengue virus preparation--48
A4: Fc-Lectin preparation--49
dc.language.isoen
dc.subject凝集素zh_TW
dc.subjectCLEC5Azh_TW
dc.subject多價zh_TW
dc.subject異元zh_TW
dc.subject複合體zh_TW
dc.subject受體zh_TW
dc.subject感染zh_TW
dc.subject病毒zh_TW
dc.subject登革zh_TW
dc.subject甘露糖zh_TW
dc.subjecthetero-complexen
dc.subjectDengue virusen
dc.subjectinfectionen
dc.subjectcooperativeen
dc.subjectinteractionen
dc.subjectmannose receptoren
dc.subjectCLEC5Aen
dc.subjectmacrophageen
dc.subjectmultivalenten
dc.subjecthetero-complexen
dc.subjectDengue virusen
dc.subjectinfectionen
dc.subjectcooperativeen
dc.subjectinteractionen
dc.subjectmannose receptoren
dc.subjectCLEC5Aen
dc.subjectmacrophageen
dc.subjectmultivalenten
dc.title登革病毒感染經由甘露糖受體與凝集素CLEC5A形成多價異元複合體zh_TW
dc.titleDengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complexen
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree博士
dc.contributor.oralexamcommittee蕭宏昇(Michael Hsiao),林宜玲(Yi-Ling Lin),吳漢忠(Han-Chung Wu),趙裕展(Yu-Chan Chao)
dc.subject.keyword登革,病毒,感染,甘露糖,受體,凝集素,CLEC5A,多價,異元,複合體,zh_TW
dc.subject.keywordDengue virus,infection,cooperative,interaction,mannose receptor,CLEC5A,macrophage,multivalent,hetero-complex,en
dc.relation.page62
dc.identifier.doi10.6342/NTU201602100
dc.rights.note有償授權
dc.date.accepted2016-08-09
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科學研究所zh_TW
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