Allison, S.L., Stadler, K., Mandl, C.W., Kunz, C., and Heinz, F.X. (1995). Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol 69, 5816-5820.
Allison, S.L., Tao, Y.J., O'Riordain, G., Mandl, C.W., Harrison, S.C., and Heinz, F.X.
(2003). Two distinct size classes of immature and mature subviral particles from tick-borne encephalitis virus. J Virol 77, 11357-11366.
Bancroft, F.W. (1906). On the influence of the relative concentration of calcium ions on the reversal of the polar effects of the galvanic current in paramecium. J Physiol 34, 444-463.
Beasley, D.W., and Barrett, A.D. (2002). Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein. J Virol 76, 13097-13100.
Brandt, W.E., McCown, J.M., Gentry, M.K., and Russell, P.K. (1982). Infection enhancement of dengue type 2 virus in the U-937 human monocyte cell line by antibodies to flavivirus cross-reactive determinants. Infect Immun 36, 1036-1041.
Bray, M., Zhao, B.T., Markoff, L., Eckels, K.H., Chanock, R.M., and Lai, C.J. (1989).
Mice immunized with recombinant vaccinia virus expressing dengue 4 virus structural proteins with or without nonstructural protein NS1 are protected against fatal dengue virus encephalitis. J Virol 63, 2853-2856.
Carey, D.E. (1971). Chikungunya and dengue: a case of mistaken identity? J Hist Med Allied Sci 26, 243-262.
Chiou, S.S., Crill, W.D., Chen, L.K., and Chang, G.J. (2008). Enzyme-linked immunosorbent assays using novel Japanese encephalitis virus antigen improve the accuracy of clinical diagnosis of flavivirus infections. Clin Vaccine Immunol 15, 825-835.
Cleaves, G.R., and Dubin, D.T. (1979). Methylation status of intracellular dengue type 2 40 S RNA. Virology 96, 159-165.
Cleland, J. B. (1918). Dengue fever in Australia: its history and clinical course, its experimental tansmission by Stegomyia fasciata, and the results of inoculation and other experiments. The Journal of hygiene 16, 317-419.
Corver, J., Ortiz, A., Allison, S.L., Schalich, J., Heinz, F.X., and Wilschut, J. (2000).
Membrane fusion activity of tick-borne encephalitis virus and recombinant subviral
particles in a liposomal model system. Virology 269, 37-46.
Crill, W.D., and Chang, G.J. (2004). Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes. J Virol 78, 13975-13986.
Crill, W.D., Hughes, H.R., Delorey, M.J., and Chang, G.J. (2009). Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens. PLoS One 4, e4991.
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.
Gould, L.H., Sui, J., Foellmer, H., Oliphant, T., Wang, T., Ledizet, M., Murakami, A., Noonan, K., Lambeth, C., Kar, K., et al. (2005). Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus. J Virol 79, 14606-14613.
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.
Gromowski, G.D., Barrett, N.D., and Barrett, A.D. (2008). Characterization of dengue virus complex-specific neutralizing epitopes on envelope protein domain III of dengue 2 virus. J Virol 82, 8828-8837.
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.
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.
Guzman, M.G., and Kouri, G. (2002). Dengue: an update. Lancet Infect Dis 2, 33-42.
Halstead, S.B. (1970). Observations related to pathogensis of dengue hemorrhagic fever.
VI. Hypotheses and discussion. Yale J Biol Med 42, 350-362.
Halstead, S.B. (1980). Dengue haemorrhagic fever--a public health problem and a field for research. Bull World Health Organ 58, 1-21.
Science 239, 476-481.
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., Venkateshan, C.N., Gentry, M.K., and Larsen, L.K. (1984).
Heterogeneity of infection enhancement of dengue 2 strains by monoclonal antibodies. J Immunol 132, 1529-1532.
Heinz, F.X. (1986). Epitope mapping of flavivirus glycoproteins. Adv Virus Res 31, 103-168.
Heinz, F.X., and Kunz, C. (1982). Molecular epidemiology of tick-borne encephalitis virus: peptide mapping of large non-structural proteins of European isolates and comparison with other flaviviruses. J Gen Virol 62 (Pt 2), 271-285.
Heinz, F.X., Stiasny, K., Puschner-Auer, G., Holzmann, H., Allison, S.L., Mandl, C.W., and Kunz, C. (1994). Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM.
Virology 198, 109-117.
Henchal, E.A., Gentry, M.K., McCown, J.M., and Brandt, W.E. (1982). Dengue virus-specific and flavivirus group determinants identified with monoclonal antibodies by indirect immunofluorescence. Am J Trop Med Hyg 31, 830-836.
Howe, G.M. (1977). A world geography of human disease. Academic Press, Inc., New York, N. Y.
Hu, H.P., Hsieh, S.C., King, C.C., and Wang, W.K. (2007). Characterization of retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope glycoproteins of four serotypes of dengue viruses. Virology 368, 376-387.
Hunt, A.R., Cropp, C.B., and Chang, G.J. (2001). A recombinant particulate antigen of Japanese encephalitis virus produced in stably-transformed cells is an effective noninfectious antigen and subunit immunogen. J Virol Methods 97, 133-149.
Kaufman, B.M., Summers, P.L., Dubois, D.R., Cohen, W.H., Gentry, M.K., Timchak, R.L., Burke, D.S., and Eckels, K.H. (1989). Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection. Am J Trop Med Hyg 41, 576-580.
Kaufman, B.M., Summers, P.L., Dubois, D.R., and Eckels, K.H. (1987). Monoclonal antibodies against dengue 2 virus E-glycoprotein protect mice against lethal dengue infection. Am J Trop Med Hyg 36, 427-434.
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.
Konishi, E., and Fujii, A. (2002). Dengue type 2 virus subviral extracellular particles produced by a stably transfected mammalian cell line and their evaluation for a subunit vaccine. Vaccine 20, 1058-1067.
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.
Lai, C.Y., Tsai, W.Y., Lin, S.R., Kao, C.L., Hu, H.P., King, C.C., Wu, H.C., Chang, G.J., and Wang, W.K. (2008). Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II. J Virol 82, 6631-6643.
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.
Lindenbach, B. D., Thiel, H. J., and Rice, C. M. (2007). Flaviviridae: the viruses and their replication. In Fields virology, D. M. Knipe and P. M. Howley, eds. (Philadelphia, Pa.: Lippincott William & Wilkins), pp. 1101-1152.
Lisova, O., Hardy, F., Petit, V., and Bedouelle, H. (2007). Mapping to completeness and transplantation of a group-specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J Gen Virol 88, 2387-2397.
Lobigs, M., Dalgarno, L., Schlesinger, J.J., and Weir, R.C. (1987). Location of a neutralization determinant in the E protein of yellow fever virus (17D vaccine strain).
Virology 161, 474-478.
Lok, S.M., Ng, M.L., and Aaskov, J. (2001). Amino acid and phenotypic changes in dengue 2 virus associated with escape from neutralisation by IgM antibody. J Med Virol
65, 315-323.
Lorenz, I.C., Kartenbeck, J., Mezzacasa, A., Allison, S.L., Heinz, F.X., and Helenius, A.
(2003). Intracellular assembly and secretion of recombinant subviral particles from tick-borne encephalitis virus. J Virol 77, 4370-4382.
Matsui, K., Gromowski, G.D., Li, L., Schuh, A.J., Lee, J.C., and Barrett, A.D. (2009).
Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III. Virology 384, 16-20.
Mazumder, R., Hu, Z.Z., Vinayaka, C.R., Sagripanti, J.L., Frost, S.D., Kosakovsky Pond, S.L., and Wu, C.H. (2007). Computational analysis and identification of amino acid sites in dengue E proteins relevant to development of diagnostics and vaccines.
Virus Genes 35, 175-186.
Men, R.H., Bray, M., and Lai, C.J. (1991). Carboxy-terminally truncated dengue virus envelope glycoproteins expressed on the cell surface and secreted extracellularly exhibit increased immunogenicity in mice. J Virol 65, 1400-1407.
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.
Modis, Y., Ogata, S., Clements, D., and Harrison, S.C. (2004). Structure of the dengue virus envelope protein after membrane fusion. Nature 427, 313-319.
Modis, Y., Ogata, S., Clements, D., and Harrison, S.C. (2005). Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol 79, 1223-1231.
Mota, J., Acosta, M., Argotte, R., Figueroa, R., Mendez, A., and Ramos, C. (2005).
Induction of protective antibodies against dengue virus by tetravalent DNA immunization of mice with domain III of the envelope protein. Vaccine 23, 3469-3476.
Mukhopadhyay, S., Kim, B.S., Chipman, P.R., Rossmann, M.G., and Kuhn, R.J. (2003).
Structure of West Nile virus. Science 302, 248.
Mukhopadhyay, S., Kuhn, R.J., and Rossmann, M.G. (2005). A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3, 13-22.
Nobuchi, H. (1979). The symptoms of a dengue-like illness recorded in a Chinese medical encyclopedia. Kanpo Rinsho 26, 422-425. (in Japanese.)
Nowak, T., Farber, P.M., and Wengler, G. (1989). Analyses of the terminal sequences of West Nile virus structural proteins and of the in vitro translation of these proteins allow the proposal of a complete scheme of the proteolytic cleavages involved in their synthesis. Virology 169, 365-376.
Nowak, T., and Wengler, G. (1987). Analysis of disulfides present in the membrane proteins of the West Nile flavivirus. Virology 156, 127-137.
Oliphant, T., Engle, M., Nybakken, G.E., Doane, C., Johnson, S., Huang, L., Gorlatov, S., Mehlhop, E., Marri, A., Chung, K.M., et al. (2005). Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Nat Med 11, 522-530.
Oliphant, T., Nybakken, G.E., Austin, S.K., Xu, Q., Bramson, J., Loeb, M., Throsby, M., Fremont, D.H., Pierson, T.C., and Diamond, M.S. (2007). Induction of epitope-specific neutralizing antibodies against West Nile virus. J Virol 81, 11828-11839.
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.
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.
Roehrig, J.T. (2003). Antigenic structure of flavivirus proteins. Adv Virus Res 59, 141-175.
Roehrig, J.T., Bolin, R.A., and Kelly, R.G. (1998). Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246, 317-328.
Roehrig, J.T., Staudinger, L.A., Hunt, A.R., Mathews, J.H., and Blair, C.D. (2001).
Antibody prophylaxis and therapy for flavivirus encephalitis infections. Ann N Y Acad Sci 951, 286-297.
Rosen, L. (1977). The Emperor's New Clothes revisited, or reflections on the pathogenesis of dengue hemorrhagic fever. Am J Trop Med Hyg 26, 337-343.
Rush, A. B. (1789). An account of the bilious remitting fever, as it appered in Philadelphia in the summer and qutumn of the year 1780. Medical enquiries and observations, p. 104-117. Prichard and Hall, Philadelphia, Pa.
Sabin, A.B., and Schlesinger, R.W. (1945). Production of Immunity to Dengue with Virus Modified by Propagation in Mice. Science 101, 640-642.
Sanchez, M.D., Pierson, T.C., McAllister, D., Hanna, S.L., Puffer, B.A., Valentine, L.E., Murtadha, M.M., Hoxie, J.A., and Doms, R.W. (2005). Characterization of neutralizing antibodies to West Nile virus. Virology 336, 70-82.
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.
Schwab, C., and Bosshard, H.R. (1992). Caveats for the use of surface-adsorbed protein antigen to test the specificity of antibodies. J Immunol Methods 147, 125-134.
Siler, J. F., Hall, M. W., and Hitchens, A. P. (1926). Dengue: its history, epidemiology,mechanism of transmission, etiology, clinical manifestations, immunity, and prevention. Philippine. J. Sci 29, 1-304.
Simmons, J. S., St John, H. F., and Reynolds, H. K. (1931). Experimental studies of dengue. Philippine. J. Sci 44, 1-251.
Smith, T. J., Brandt, W. E., Swanson, J. L., McCown, J. M., and Buescher, E. L. (1970).
Physical and biological properties of dengue-2 virus and associated antigens. J. Virol. 5, 524-532
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.
Thali, M., Furman, C., Ho, D.D., Robinson, J., Tilley, S., Pinter, A., and Sodroski, J.
(1992). Discontinuous, conserved neutralization epitopes overlapping the CD4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein. J Virol
66, 5635-5641.
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.
Vogt, M.R., Moesker, B., Goudsmit, J., Jongeneelen, M., Austin, S.K., Oliphant, T., Nelson, S., Pierson, T.C., Wilschut, J., Throsby, M., et al. (2009). Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step. J Virol 83, 6494-6507.
Volk, D.E., Beasley, D.W., Kallick, D.A., Holbrook, M.R., Barrett, A.D., and Gorenstein, D.G. (2004). Solution structure and antibody binding studies of the envelope protein domain III from the New York strain of West Nile virus. J Biol Chem
279, 38755-38761.
Wengler, G., and Gross, H.J. (1978). Studies on virus-specific nucleic acids synthesized in vertebrate and mosquito cells infected with flaviviruses. Virology 89, 423-437.
Yu, S., Wuu, A., Basu, R., Holbrook, M.R., Barrett, A.D., and Lee, J.C. (2004).
Solution structure and structural dynamics of envelope protein domain III of mosquito- and tick-borne flaviviruses. Biochemistry 43, 9168-9176.
表一、構築質體所使用的引子序列
primer Sequence 5'→3'
D3E17GA GGAAGGTCTGTCAGCAGCTACGTGGGTTG
圖一、表現 DENV3 PrM/E 蛋白質之質體及 E 蛋白質 alanine 單點置換突 變之質體。
圖二、表現單點突變之 DENV3 E 蛋白質。轉染 DENV3 之 E 蛋白質 alanine 單點突變質體至293T 細胞,48 小時後收集 cell lysates,以 mixed mAbs (包 含flavivirus group-reactive、DENV complex-reactive 及 DENV3 type-specific 三種單株抗體的混合物)為一級抗體,進行西方墨點分析法,調整 cell lysates 濃度,利用影像分析軟體UVP 定量 E band intensity,確認各個 E mutant /wt E 值約為 1.0。
圖三、alanine 單點突變之 DENV3 E 蛋白質對於 flavivirus group-reactive 單株抗體結合能力的影響。(A) 4G2;(B) FL0231;(C) FL0232。利用上述 方法調整好的cell lysates 濃度,以不同老鼠單株抗體為一級抗體,進行西 方墨點法分析。Recognition Index 計算方式如下:[ Intensity of mutant E/ wt E] mAb / [ Intensity of mutant E/ wt E] miexd mAbs。
圖四、E 蛋白質 fusion loop 區域之單點突變對於 flavivirus group-reactive 單株抗體結合能力的影響。比較各單株抗體對 DENV3 ( A、B、C ) 及 DENV1 ( D、E、F )的 fusion loop 胺基酸單點突變結合能力之異同。
圖五、alanine 單點突變之 DENV3 E 蛋白質對於 complex/ subcomplex-reactive 單株抗體結合能力的影響。(A) DC7-3;(B) DC9-6;(C) DC12-3。
圖六、alanine 單點突變之 DENV3 E 蛋白質對 DENV3 type-specific 單株 抗體 DC6-3 結合能力的影響。
圖七、不同種類之老鼠單株抗體對於
DENV3 E
蛋白質及DENV1 E
蛋白質上的抗體 辨識部位之比較。圖八、感染 DENV3 之 DF 病人血清,包括初次感染以及二次感染之病人。
* DF 發病日與採血日之間隔。
圖九、alanine 單點突變之 DENV3 E 蛋白質對 DENV3 初次感染之 DF 病 人 ( DF89-2008 ) 血清中抗 E 抗體結合能力的影響。
圖十、alanine 單點突變之 DENV3 E 蛋白質對二次感染 DENV3 之 DF 病 人血清中抗 E 抗體結合能力的影響。(A) DF70-2008;(B) DF95-2008;(C) DF98-2008;(D) DF90-2008;(E) DF71-2008。
圖十一、alanine 單點突變之 DENV3 E 蛋白質對二次感染 DENV3 之 DF 病人血清中抗 E 抗體結合能力的影響。(A) DF87-2008;(B) DF92-2008;
(C) DF102-2008;(D) DF104-2008。
圖十二、alanine fusion loop 及 domain III 多點突變之 VLPs 對 DF 病人血 清中抗 E 抗體結合能力的影響。轉染 DENV3 之 E 蛋白質 alanine fusion loop 及 domain III 多點突變質體至 293T 細胞,48 小時後收集上清液以超高速 離心分離出VLPs,進行 capture ELISA。(A) 以 mixed mAbs 為一級抗體,
利用capture ELISA 進行定量,調整各個 VLPs 濃度使 OD450-650 讀值約 為1.0,之後以 DF 病人血清為一級抗體,進行 capture ELISA 分析;(B) fusion loop 區域多點突變(中間)與 domain III 多點突變之 E 蛋白質(右)對於 DF
病人血清中抗 E 抗體結合能力的影響,其分析結果與西方墨點分析法之
結果(左)有相同趨勢;(C) DF 病人血清中辨識 E 蛋白質之 101W、106G 和 108F 之抗體比例;proportion (%) = (1-[mutant VLPs endpoint titer/wt VLPs endpoint titer])*100%。
圖十三、alanine fusion loop 多點突變之 VLPs 對 DF 病人血清中抗 E 抗體 結合能力的影響。 (A) fusion loop 區域多點突變之 E 蛋白質對於其他 DF 病人血清中抗E 抗體結合能力的影響;(B) DF 病人血清中辨識 E 蛋白質 之101W、106G 和 108F 之抗體比例,proportion (%) = (1-[mutant VLPs endpoint titer/wt VLPs endpoint titer])*100%。