簡易檢索 / 詳目顯示

研究生: 沈文凡
Wen-Fan Shen
論文名稱: 第四型登革病毒單株抗體之特性探討
Characterization of Monoclonal Antibodies against Dengue Virus Type 4
指導教授: 吳漢忠
Wu, Han-Chung
童麗珠
Tung, Li-Chu
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2009
畢業學年度: 97
語文別: 英文
論文頁數: 71
中文關鍵詞: 登革病毒套膜蛋白單株抗體抗原決定位DNA疫苗
英文關鍵詞: dengue virus, envelope protein, monoclonal antibody, epitopes, DNA vaccine
論文種類: 學術論文
相關次數: 點閱:140下載:2
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 登革病毒是盛行於熱帶及亞熱帶地區感染人類的病原體,主要的傳染途徑是經由帶有病毒的病媒蚊叮咬,後而易引起登革熱、登革出血熱和登革休克症候。登革病毒的套膜蛋白[envelope (E) protein]具有結合細胞表面受器及引發病毒與宿主間膜融合的功能,同時亦是能誘發人體免疫反應的重要抗原;套膜蛋白的膜外區域(E domain)可以再進一步區分為三個功能區塊:區塊一、區塊二與區塊三(EDI, II, III)。為了探究登革病毒中和性抗體之抗原決定位及未來研發登革的DNA疫苗,本研究篩選了若干株由我們實驗室所生產的抗體,以釐清第四型登革病毒與中和性抗體之間的交互作用。作法上,我們先利用免疫光染色法與西方墨點法來確認單株抗體的專一性,並且找到若干株單株抗體能對抗病毒的套模蛋白或非結構性蛋白一[Non-structural (NS)-1]。我們更進一步利用蝕斑減少中和試驗[Plaque reduction neutralization test (PRNT)],與保護試驗檢測這些單株抗體對於登革第四型的中和能力。我們亦製造了兩個DNA載體,分別含有第四型登革病毒的功能區塊一、二及三,並將此載體利用基因槍施打於小鼠身上,希望能藉此比較功能區塊一、二及功能區塊三對於誘發免疫反應的能力。我們亦施打第四型登革病毒DNA疫苗,pCB8D4-2J,及我們製作的載體,進一步比較並評估該製造的載體是否有成為DNA疫苗的潛力。在本實驗中我們t辨識出九株單株抗體能專一辨識第四型登革病毒與九株會變其他型登革病毒的單株抗體;其中有十四株抗體是辨識套模蛋白,兩株是辨識非結構性蛋白一。在辨識套模蛋白中,有七株單株抗體是辨識區塊一、二,另有兩株抗體能辨識區塊三。最後找到兩株能辨識登革第四型功能區塊一、二,並在細胞實驗上能阻止病毒感染,但只有一株抗體能在動物模式上提供保護。同時我們製造的DNA疫苗,雖然能夠表現其蛋白質於細胞且被抗體所辨識,但是在誘發對抗登革病毒免疫的能力上,仍不及pCB8D4-2J;顯示該DNA疫苗需多次免疫方能有效誘導出對抗登革病毒的抗體。

    Dengue virus (DENV), the human pathogen leading to dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), is epidemic in tropical and subtropical areas around the world. The envelope protein (E) of DENV, which could induce protective immunity, is critical for membrane fusion and mediates binding to cellular receptors. The ectodomain of the E monomer could further be divided into three domains assigned to domain I, domain II and domain III (EDI, EDII and EDIII). In order to confirm the target of neutralizing antibodies and develop the DNA vaccines of DENV, we generated a large panel of MAbs against DENV4 in our laboratory. In our study, we further these MAbs against DENV4. At first, we use the immunofluorescence and Western blotting to identify the specificity of those MAbs. Several MAbs could recognize the envelop protein (E protein) or non-structural protein 1 (NS-1). We further demonstrated their neutralizing activity of DENV4 by plaque reduction neutralization test (PRNT) and protection assay. We have identified 9 serotype-specific MAbs and 9 cross-reactive MAbs against DENV4, and 14 MAbs could recognize E protein and 2 MAbs recognized NS-1 protein. Among these MAb recognized E protein, seven MAbs could recognize EDI-II and 2 MAbs recognized EDIII. Finally, we identified 2 MAbs, which recognized EDI-II of DENV4, displayed neutralizing activity in vitro, but only one MAb could reveal protective activity in vivo. We also constructed two DNA vectors which contained the EDI-II and EDIII of DENV4, and immunized the mice for identification the neutralizing antibodies. We used the DNA vaccine of DENV4, pCB8D4-2J, to immunize the mice to determine the neutralizing avtivity of EDI-II or EDIII DNA vaccine by PRNT and protection assay for imitating immune responses against DENV4 in vitro and in vivo. Although the two DNA vaccines, EDI-II and EDIII, could be detected the protein by IFA, their humoral immunity against DENV4 still weaker than pCB8D4-2J. It might result from less immunization, so we need to immunize mice more times.

    中文摘要………………………………………………………………2 Abstract………………………………………………………………4 致謝……………………………………………………………………6 Contents………………………………………………………………7 Introduction…………………………………………………………8 Materials and Methods……………………………………………22 Results………………………………………………………………28 Discuession…………………………………………………………34 Figure………………………………………………………………39 Table…………………………………………………………………55 Reference……………………………………………………………56

    Aaskov, J.G., Geysen, H.M., and Mason, T.J. (1989). Serologically defined linear epitopes in the envelope protein of dengue 2 (Jamaica strain 1409). Arch Virol 105, 209-221.
    Agarwal, R., Elbishbishi, E.A., Chaturvedi, U.C., Nagar, R., and Mustafa, A.S. (1999). Profile of transforming growth factor-beta 1 in patients with dengue haemorrhagic fever. Int J Exp Pathol 80, 143-149.
    Allison, S.L., Schalich, J., Stiasny, K., Mandl, C.W., and Heinz, F.X. (2001). Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75, 4268-4275.
    Allison, S.L., Schalich, J., Stiasny, K., Mandl, C.W., Kunz, C., and Heinz, F.X. (1995). Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69, 695-700.
    Alvarez, D.E., De Lella Ezcurra, A.L., Fucito, S., and Gamarnik, A.V. (2005). Role of RNA structures present at the 3'UTR of dengue virus on translation, RNA synthesis, and viral replication. Virology 339, 200-212.
    Anderson, R., Wang, S., Osiowy, C., and Issekutz, A.C. (1997). Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J Virol 71, 4226-4232.
    Azeredo, E.L., De Oliveira-Pinto, L.M., Zagne, S.M., Cerqueira, D.I., Nogueira, R.M., and Kubelka, C.F. (2006). NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease. Clin Exp Immunol 143, 345-356.
    Balmaseda, A., Hammond, S.N., Perez, L., Tellez, Y., Saborio, S.I., Mercado, J.C., Cuadra, R., Rocha, J., Perez, M.A., Silva, S., et al. (2006). Serotype-specific differences in clinical manifestations of dengue. Am J Trop Med Hyg 74, 449-456.
    Braga, E.L., Moura, P., Pinto, L.M., Ignacio, S.R., Oliveira, M.J., Cordeiro, M.T., and Kubelka, C.F. (2001). Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever. Mem Inst Oswaldo Cruz 96, 229-232.
    Brinton, M.A. (2002). The molecular biology of West Nile Virus: a new invader of the western hemisphere. Annu Rev Microbiol 56, 371-402.
    Chakravarti, A., and Kumaria, R. (2006). Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak. Indian J Med Res 123, 25-30.
    Chambers, T.J., Hahn, C.S., Galler, R., and Rice, C.M. (1990). Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44, 649-688.
    Chang, G.J., Hunt, A.R., Holmes, D.A., Springfield, T., Chiueh, T.S., Roehrig, J.T., and Gubler, D.J. (2003). Enhancing biosynthesis and secretion of premembrane and envelope proteins by the chimeric plasmid of dengue virus type 2 and Japanese encephalitis virus. Virology 306, 170-180.
    Chareonsirisuthigul, T., Kalayanarooj, S., and Ubol, S. (2007). Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. J Gen Virol 88, 365-375.
    Chaturvedi, U.C., Shrivastava, R., Tripathi, R.K., and Nagar, R. (2007). Dengue virus-specific suppressor T cells: current perspectives. FEMS Immunol Med Microbiol 50, 285-299.
    Chen, L.C., Lei, H.Y., Liu, C.C., Shiesh, S.C., Chen, S.H., Liu, H.S., Lin, Y.S., Wang, S.T., Shyu, H.W., and Yeh, T.M. (2006). Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. Am J Trop Med Hyg 74, 142-147.
    Chen, Y., Maguire, T., Hileman, R.E., Fromm, J.R., Esko, J.D., Linhardt, R.J., and Marks, R.M. (1997). Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med 3, 866-871.
    Chen, Y.C., Wang, S.Y., and King, C.C. (1999). Bacterial lipopolysaccharide inhibits dengue virus infection of primary human monocytes/macrophages by blockade of virus entry via a CD14-dependent mechanism. J Virol 73, 2650-2657.
    Chiu, M.W., and Yang, Y.L. (2003). Blocking the dengue virus 2 infections on BHK-21 cells with purified recombinant dengue virus 2 E protein expressed in Escherichia coli. Biochem Biophys Res Commun 309, 672-678.
    Chiu, W.W., Kinney, R.M., and Dreher, T.W. (2005). Control of translation by the 5'- and 3'-terminal regions of the dengue virus genome. J Virol 79, 8303-8315.
    Crill, W.D., and Roehrig, J.T. (2001). Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol 75, 7769-7773.
    Cummings, D.A., Schwartz, I.B., Billings, L., Shaw, L.B., and Burke, D.S. (2005). Dynamic effects of antibody-dependent enhancement on the fitness of viruses. Proc Natl Acad Sci U S A 102, 15259-15264.
    De Paula, S.O., Lima, D.M., de Oliveira Franca, R.F., Gomes-Ruiz, A.C., and da Fonseca, B.A. (2008). A DNA vaccine candidate expressing dengue-3 virus prM and E proteins elicits neutralizing antibodies and protects mice against lethal challenge. Arch Virol 153, 2215-2223.
    Degli-Esposti, M.A., and Smyth, M.J. (2005). Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5, 112-124.
    Diamond, M.S., Roberts, T.G., Edgil, D., Lu, B., Ernst, J., and Harris, E. (2000). Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons. J Virol 74, 4957-4966.
    Eckels, K.H., Scott, R.M., Bancroft, W.H., Brown, J., Dubois, D.R., Summers, P.L., Russell, P.K., and Halstead, S.B. (1984). Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. V. Human response to immunization with a candidate vaccine prepared in fetal rhesus lung cells. Am J Trop Med Hyg 33, 684-689.
    Elshuber, S., Allison, S.L., Heinz, F.X., and Mandl, C.W. (2003). Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J Gen Virol 84, 183-191.
    Falconar, A.K. (1999). Identification of an epitope on the dengue virus membrane (M) protein defined by cross-protective monoclonal antibodies: design of an improved epitope sequence based on common determinants present in both envelope (E and M) proteins. Arch Virol 144, 2313-2330.
    Goncalvez, A.P., Purcell, R.H., and Lai, C.J. (2004). Epitope determinants of a chimpanzee Fab antibody that efficiently cross-neutralizes dengue type 1 and type 2 viruses map to inside and in close proximity to fusion loop of the dengue type 2 virus envelope glycoprotein. J Virol 78, 12919-12928.
    Gromowski, G.D., and Barrett, A.D. (2007). Characterization of an antigenic site that contains a dominant, type-specific neutralization determinant on the envelope protein domain III (ED3) of dengue 2 virus. Virology 366, 349-360.
    Gubler, D.J. (1998). Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11, 480-496.
    Gubler, D.J. (2002). Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 10, 100-103.
    Gubler, D.J. (2006). Dengue/dengue haemorrhagic fever: history and current status. Novartis Found Symp 277, 3-16; discussion 16-22, 71-13, 251-253.
    Guirakhoo, F., Arroyo, J., Pugachev, K.V., Miller, C., Zhang, Z.X., Weltzin, R., Georgakopoulos, K., Catalan, J., Ocran, S., Soike, K., et al. (2001). Construction, safety, and immunogenicity in nonhuman primates of a chimeric yellow fever-dengue virus tetravalent vaccine. J Virol 75, 7290-7304.
    Guirakhoo, F., Bolin, R.A., and Roehrig, J.T. (1992). The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein. Virology 191, 921-931.
    Guirakhoo, F., Heinz, F.X., Mandl, C.W., Holzmann, H., and Kunz, C. (1991). Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions. J Gen Virol 72 ( Pt 6), 1323-1329.
    Guirakhoo, F., Kitchener, S., Morrison, D., Forrat, R., McCarthy, K., Nichols, R., Yoksan, S., Duan, X., Ermak, T.H., Kanesa-Thasan, N., et al. (2006). Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax-DEN2) vaccine: Phase I clinical trial for safety and immunogenicity: effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes. Hum Vaccin 2, 60-67.
    Guirakhoo, F., Pugachev, K., Arroyo, J., Miller, C., Zhang, Z.X., Weltzin, R., Georgakopoulos, K., Catalan, J., Ocran, S., Draper, K., et al. (2002). Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates. Virology 298, 146-159.
    Guzman, M.G., Rodriguez, R., Hermida, L., Alvarez, M., Lazo, L., Mune, M., Rosario, D., Valdes, K., Vazquez, S., Martinez, R., et al. (2003). Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris. Am J Trop Med Hyg 69, 129-134.
    Halstead, S.B. (1983). Dengue haemorrhagic fever. Trans R Soc Trop Med Hyg 77, 739-740.
    Halstead, S.B. (1990). Global epidemiology of dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health 21, 636-641.
    Halstead, S.B. (2003). Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60, 421-467.
    Halstead, S.B., and O'Rourke, E.J. (1977). Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146, 201-217.
    Halstead, S.B., O'Rourke, E.J., and Allison, A.C. (1977). Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. J Exp Med 146, 218-229.
    Halstead, S.B., Rojanasuphot, S., and Sangkawibha, N. (1983). Original antigenic sin in dengue. Am J Trop Med Hyg 32, 154-156.
    Henchal, E.A., and Putnak, J.R. (1990). The dengue viruses. Clin Microbiol Rev 3, 376-396.
    Higgs, S., Vanlandingham, D.L., Klingler, K.A., McElroy, K.L., McGee, C.E., Harrington, L., Lang, J., Monath, T.P., and Guirakhoo, F. (2006). Growth characteristics of ChimeriVax-Den vaccine viruses in Aedes aegypti and Aedes albopictus from Thailand. Am J Trop Med Hyg 75, 986-993.
    Hilleman, M.R. (2004). Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections. Proc Natl Acad Sci U S A 101 Suppl 2, 14560-14566.
    Hiramatsu, K., Tadano, M., Men, R., and Lai, C.J. (1996). Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2) envelope protein: monoclonal antibody resistant DEN2/DEN4 chimeras exhibit reduced mouse neurovirulence. Virology 224, 437-445.
    Ho, L.J., Hung, L.F., Weng, C.Y., Wu, W.L., Chou, P., Lin, Y.L., Chang, D.M., Tai, T.Y., and Lai, J.H. (2005). Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell. J Immunol 174, 8163-8172.
    Hober, D., Delannoy, A.S., Benyoucef, S., De Groote, D., and Wattre, P. (1996). High levels of sTNFR p75 and TNF alpha in dengue-infected patients. Microbiol Immunol 40, 569-573.
    Huang, K.J., Yang, Y.C., Lin, Y.S., Huang, J.H., Liu, H.S., Yeh, T.M., Chen, S.H., Liu, C.C., and Lei, H.Y. (2006). The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection. J Immunol 176, 2825-2832.
    Huang, L., and Shi, Y. (2001). Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol. Chin Med J (Engl) 114, 628-631.
    Hung, S.L., Lee, P.L., Chen, H.W., Chen, L.K., Kao, C.L., and King, C.C. (1999). Analysis of the steps involved in Dengue virus entry into host cells. Virology 257, 156-167.
    Jaiswal, S., Khanna, N., and Swaminathan, S. (2004). High-level expression and one-step purification of recombinant dengue virus type 2 envelope domain III protein in Escherichia coli. Protein Expr Purif 33, 80-91.
    Jindadamrongwech, S., Thepparit, C., and Smith, D.R. (2004). Identification of GRP 78 (BiP) as a liver cell expressed receptor element for dengue virus serotype 2. Arch Virol 149, 915-927.
    Jones, C.T., Ma, L., Burgner, J.W., Groesch, T.D., Post, C.B., and Kuhn, R.J. (2003). Flavivirus capsid is a dimeric alpha-helical protein. J Virol 77, 7143-7149.
    Kanai, R., Kar, K., Anthony, K., Gould, L.H., Ledizet, M., Fikrig, E., Marasco, W.A., Koski, R.A., and Modis, Y. (2006). Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes. J Virol 80, 11000-11008.
    Kautner, I., Robinson, M.J., and Kuhnle, U. (1997). Dengue virus infection: epidemiology, pathogenesis, clinical presentation, diagnosis, and prevention. J Pediatr 131, 516-524.
    Kiermayr, S., Kofler, R.M., Mandl, C.W., Messner, P., and Heinz, F.X. (2004). Isolation of capsid protein dimers from the tick-borne encephalitis flavivirus and in vitro assembly of capsid-like particles. J Virol 78, 8078-8084.
    Kliks, S.C., Nisalak, A., Brandt, W.E., Wahl, L., and Burke, D.S. (1989). Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 40, 444-451.
    Kochel, T., Wu, S.J., Raviprakash, K., Hobart, P., Hoffman, S., Porter, K., and Hayes, C. (1997). Inoculation of plasmids expressing the dengue-2 envelope gene elicit neutralizing antibodies in mice. Vaccine 15, 547-552.
    Kuhn, R.J., Zhang, W., Rossmann, M.G., Pletnev, S.V., Corver, J., Lenches, E., Jones, C.T., Mukhopadhyay, S., Chipman, P.R., Strauss, E.G., et al. (2002). Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717-725.
    Kurane, I., Innis, B.L., Nimmannitya, S., Nisalak, A., Meager, A., and Ennis, F.A. (1993). High levels of interferon alpha in the sera of children with dengue virus infection. Am J Trop Med Hyg 48, 222-229.
    Kurane, I., Innis, B.L., Nimmannitya, S., Nisalak, A., Meager, A., Janus, J., and Ennis, F.A. (1991). Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. J Clin Invest 88, 1473-1480.
    Laoprasopwattana, K., Libraty, D.H., Endy, T.P., Nisalak, A., Chunsuttiwat, S., Vaughn, D.W., Reed, G., Ennis, F.A., Rothman, A.L., and Green, S. (2005). Dengue Virus (DV) enhancing antibody activity in preillness plasma does not predict subsequent disease severity or viremia in secondary DV infection. J Infect Dis 192, 510-519.
    Lin, B., Parrish, C.R., Murray, J.M., and Wright, P.J. (1994). Localization of a neutralizing epitope on the envelope protein of dengue virus type 2. Virology 202, 885-890.
    Lin, Y.S., Lin, C.F., Lei, H.Y., Liu, H.S., Yeh, T.M., Chen, S.H., and Liu, C.C. (2004). Antibody-mediated endothelial cell damage via nitric oxide. Curr Pharm Des 10, 213-221.
    Lindenbach, B.D., and Rice, C.M. (2003). Molecular biology of flaviviruses. Adv Virus Res 59, 23-61.
    Littaua, R., Kurane, I., and Ennis, F.A. (1990). Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144, 3183-3186.
    Lorenz, I.C., Allison, S.L., Heinz, F.X., and Helenius, A. (2002). Folding and dimerization of tick-borne encephalitis virus envelope proteins prM and E in the endoplasmic reticulum. J Virol 76, 5480-5491.
    Lozach, P.Y., Burleigh, L., Staropoli, I., Navarro-Sanchez, E., Harriague, J., Virelizier, J.L., Rey, F.A., Despres, P., Arenzana-Seisdedos, F., and Amara, A. (2005). Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)-mediated enhancement of dengue virus infection is independent of DC-SIGN internalization signals. J Biol Chem 280, 23698-23708.
    Mady, B.J., Erbe, D.V., Kurane, I., Fanger, M.W., and Ennis, F.A. (1991). Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. J Immunol 147, 3139-3144.
    Mady, B.J., Kurane, I., Erbe, D.V., Fanger, M.W., and Ennis, F.A. (1993). Neuraminidase augments Fc gamma receptor II-mediated antibody-dependent enhancement of dengue virus infection. J Gen Virol 74 ( Pt 5), 839-844.
    Medin, C.L., Fitzgerald, K.A., and Rothman, A.L. (2005). Dengue virus nonstructural protein NS5 induces interleukin-8 transcription and secretion. J Virol 79, 11053-11061.
    Megret, F., Hugnot, J.P., Falconar, A., Gentry, M.K., Morens, D.M., Murray, J.M., Schlesinger, J.J., Wright, P.J., Young, P., Van Regenmortel, M.H., et al. (1992). Use of recombinant fusion proteins and monoclonal antibodies to define linear and discontinuous antigenic sites on the dengue virus envelope glycoprotein. Virology 187, 480-491.
    Messer, W.B., Gubler, D.J., Harris, E., Sivananthan, K., and de Silva, A.M. (2003). Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis 9, 800-809.
    Modis, Y., Ogata, S., Clements, D., and Harrison, S.C. (2003). A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A 100, 6986-6991.
    Monath, T.P. (1994). Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 91, 2395-2400.
    Mongkolsapaya, J., Duangchinda, T., Dejnirattisai, W., Vasanawathana, S., Avirutnan, P., Jairungsri, A., Khemnu, N., Tangthawornchaikul, N., Chotiyarnwong, P., Sae-Jang, K., et al. (2006). T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal? J Immunol 176, 3821-3829.
    Morens, D.M., Halstead, S.B., Repik, P.M., Putvatana, R., and Raybourne, N. (1985). Simplified plaque reduction neutralization assay for dengue viruses by semimicro methods in BHK-21 cells: comparison of the BHK suspension test with standard plaque reduction neutralization. J Clin Microbiol 22, 250-254.
    Mukerjee, R., Misra, A., and Chaturvedi, U.C. (1996). Dengue virus-induced cytotoxin releases nitrite by spleen cells. Int J Exp Pathol 77, 45-51.
    Mukhopadhyay, S., Kim, B.S., Chipman, P.R., Rossmann, M.G., and Kuhn, R.J. (2003). Structure of West Nile virus. Science 302, 248.
    Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J.L., Arenzana-Seisdedos, F., and Despres, P. (2003). Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep 4, 723-728.
    Neves-Souza, P.C., Azeredo, E.L., Zagne, S.M., Valls-de-Souza, R., Reis, S.R., Cerqueira, D.I., Nogueira, R.M., and Kubelka, C.F. (2005). Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection. BMC Infect Dis 5, 64.
    Ocazionez Jimenez, R., and Lopes da Fonseca, B.A. (2000). Recombinant plasmid expressing a truncated dengue-2 virus E protein without co-expression of prM protein induces partial protection in mice. Vaccine 19, 648-654.
    Oliphant, T., Nybakken, G.E., Engle, M., Xu, Q., Nelson, C.A., Sukupolvi-Petty, S., Marri, A., Lachmi, B.E., Olshevsky, U., Fremont, D.H., et al. (2006). Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein. J Virol 80, 12149-12159.
    Palmer, C.J., King, S.D., Cuadrado, R.R., Perez, E., Baum, M., and Ager, A.L. (1999). Evaluation of the MRL diagnostics dengue fever virus IgM capture ELISA and the PanBio Rapid Immunochromatographic Test for diagnosis of dengue fever in Jamaica. J Clin Microbiol 37, 1600-1601.
    Perez, A.B., Garcia, G., Sierra, B., Alvarez, M., Vazquez, S., Cabrera, M.V., Rodriguez, R., Rosario, D., Martinez, E., Denny, T., et al. (2004). IL-10 levels in Dengue patients: some findings from the exceptional epidemiological conditions in Cuba. J Med Virol 73, 230-234.
    Pierson, T.C., Xu, Q., Nelson, S., Oliphant, T., Nybakken, G.E., Fremont, D.H., and Diamond, M.S. (2007). The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe 1, 135-145.
    Pokidysheva, E., Zhang, Y., Battisti, A.J., Bator-Kelly, C.M., Chipman, P.R., Xiao, C., Gregorio, G.G., Hendrickson, W.A., Kuhn, R.J., and Rossmann, M.G. (2006). Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell 124, 485-493.
    Putnak, R., Barvir, D.A., Burrous, J.M., Dubois, D.R., D'Andrea, V.M., Hoke, C.H., Sadoff, J.C., and Eckels, K.H. (1996a). Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys. J Infect Dis 174, 1176-1184.
    Putnak, R., Cassidy, K., Conforti, N., Lee, R., Sollazzo, D., Truong, T., Ing, E., Dubois, D., Sparkuhl, J., Gastle, W., et al. (1996b). Immunogenic and protective response in mice immunized with a purified, inactivated, Dengue-2 virus vaccine prototype made in fetal rhesus lung cells. Am J Trop Med Hyg 55, 504-510.
    Rabablert, J., and Yoksan, S. (2009). Attenuated D2 16681-PDK53 vaccine: defining humoral and cell-mediated immunity. Curr Pharm Des 15, 1203-1211.
    Raghupathy, R., Chaturvedi, U.C., Al-Sayer, H., Elbishbishi, E.A., Agarwal, R., Nagar, R., Kapoor, S., Misra, A., Mathur, A., Nusrat, H., et al. (1998). Elevated levels of IL-8 in dengue hemorrhagic fever. J Med Virol 56, 280-285.
    Raviprakash, K., Ewing, D., Simmons, M., Porter, K.R., Jones, T.R., Hayes, C.G., Stout, R., and Murphy, G.S. (2003). Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys. Virology 315, 345-352.
    Raviprakash, K., Marques, E., Ewing, D., Lu, Y., Phillips, I., Porter, K.R., Kochel, T.J., August, T.J., Hayes, C.G., and Murphy, G.S. (2001). Synergistic neutralizing antibody response to a dengue virus type 2 DNA vaccine by incorporation of lysosome-associated membrane protein sequences and use of plasmid expressing GM-CSF. Virology 290, 74-82.
    Raviprakash, K., Porter, K.R., Kochel, T.J., Ewing, D., Simmons, M., Phillips, I., Murphy, G.S., Weiss, W.R., and Hayes, C.G. (2000). Dengue virus type 1 DNA vaccine induces protective immune responses in rhesus macaques. J Gen Virol 81, 1659-1667.
    Rey, F.A., Heinz, F.X., Mandl, C., Kunz, C., and Harrison, S.C. (1995). The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375, 291-298.
    Reyes-Del Valle, J., Chavez-Salinas, S., Medina, F., and Del Angel, R.M. (2005). Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells. J Virol 79, 4557-4567.
    Rico-Hesse, R., Harrison, L.M., Salas, R.A., Tovar, D., Nisalak, A., Ramos, C., Boshell, J., de Mesa, M.T., Nogueira, R.M., and da Rosa, A.T. (1997). Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology 230, 244-251.
    Robert Putnak, J., Coller, B.A., Voss, G., Vaughn, D.W., Clements, D., Peters, I., Bignami, G., Houng, H.S., Chen, R.C., Barvir, D.A., et al. (2005). An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model. Vaccine 23, 4442-4452.
    Roehrig, J.T. (2003). Antigenic structure of flavivirus proteins. Adv Virus Res 59, 141-175.
    Sabin, A.B. (1952). Research on dengue during World War II. Am J Trop Med Hyg 1, 30-50.
    Sangkawibha, N., Rojanasuphot, S., Ahandrik, S., Viriyapongse, S., Jatanasen, S., Salitul, V., Phanthumachinda, B., and Halstead, S.B. (1984). Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol 120, 653-669.
    Schalich, J., Allison, S.L., Stiasny, K., Mandl, C.W., Kunz, C., and Heinz, F.X. (1996). Recombinant subviral particles from tick-borne encephalitis virus are fusogenic and provide a model system for studying flavivirus envelope glycoprotein functions. J Virol 70, 4549-4557.
    Serafin, I.L., and Aaskov, J.G. (2001). Identification of epitopes on the envelope (E) protein of dengue 2 and dengue 3 viruses using monoclonal antibodies. Arch Virol 146, 2469-2479.
    Simmons, C.P., Popper, S., Dolocek, C., Chau, T.N., Griffiths, M., Dung, N.T., Long, T.H., Hoang, D.M., Chau, N.V., Thao le, T.T., et al. (2007). Patterns of host genome-wide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever. J Infect Dis 195, 1097-1107.
    Stadler, K., Allison, S.L., Schalich, J., and Heinz, F.X. (1997). Proteolytic activation of tick-borne encephalitis virus by furin. J Virol 71, 8475-8481.
    Stiasny, K., Kiermayr, S., Holzmann, H., and Heinz, F.X. (2006). Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic sites. J Virol 80, 9557-9568.
    Sukupolvi-Petty, S., Austin, S.K., Purtha, W.E., Oliphant, T., Nybakken, G.E., Schlesinger, J.J., Roehrig, J.T., Gromowski, G.D., Barrett, A.D., Fremont, D.H., et al. (2007). Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. J Virol 81, 12816-12826.
    Sun, W., Edelman, R., Kanesa-Thasan, N., Eckels, K.H., Putnak, J.R., King, A.D., Houng, H.S., Tang, D., Scherer, J.M., Hoke, C.H., Jr., et al. (2003). Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates. Am J Trop Med Hyg 69, 24-31.
    Takhampunya, R., Padmanabhan, R., and Ubol, S. (2006). Antiviral action of nitric oxide on dengue virus type 2 replication. J Gen Virol 87, 3003-3011.
    Talavera, D., Castillo, A.M., Dominguez, M.C., Gutierrez, A.E., and Meza, I. (2004). IL8 release, tight junction and cytoskeleton dynamic reorganization conducive to permeability increase are induced by dengue virus infection of microvascular endothelial monolayers. J Gen Virol 85, 1801-1813.
    Tassaneetrithep, B., Burgess, T.H., Granelli-Piperno, A., Trumpfheller, C., Finke, J., Sun, W., Eller, M.A., Pattanapanyasat, K., Sarasombath, S., Birx, D.L., et al. (2003). DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med 197, 823-829.
    Thein, S., Aung, M.M., Shwe, T.N., Aye, M., Zaw, A., Aye, K., Aye, K.M., and Aaskov, J. (1997). Risk factors in dengue shock syndrome. Am J Trop Med Hyg 56, 566-572.
    Thepparit, C., and Smith, D.R. (2004). Serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor. J Virol 78, 12647-12656.
    Throsby, M., Geuijen, C., Goudsmit, J., Bakker, A.Q., Korimbocus, J., Kramer, R.A., Clijsters-van der Horst, M., de Jong, M., Jongeneelen, M., Thijsse, S., et al. (2006). Isolation and characterization of human monoclonal antibodies from individuals infected with West Nile Virus. J Virol 80, 6982-6992.
    Trainor, N.B., Crill, W.D., Roberson, J.A., and Chang, G.J. (2007). Mutation analysis of the fusion domain region of St. Louis encephalitis virus envelope protein. Virology 360, 398-406.
    van Den Broek, M., Bachmann, M.F., Kohler, G., Barner, M., Escher, R., Zinkernagel, R., and Kopf, M. (2000). IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-gamma and nitric oxide synthetase 2. J Immunol 164, 371-378.
    van Der Most, R.G., Murali-Krishna, K., Ahmed, R., and Strauss, J.H. (2000). Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response. J Virol 74, 8094-8101.
    Wang, E., Ni, H., Xu, R., Barrett, A.D., Watowich, S.J., Gubler, D.J., and Weaver, S.C. (2000). Evolutionary relationships of endemic/epidemic and sylvatic dengue viruses. J Virol 74, 3227-3234.
    Zhang, Y., Zhang, W., Ogata, S., Clements, D., Strauss, J.H., Baker, T.S., Kuhn, R.J., and Rossmann, M.G. (2004). Conformational changes of the flavivirus E glycoprotein. Structure 12, 1607-1618.

    下載圖示
    QR CODE