請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9329
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王維恭(Wei-Kung Wang) | |
dc.contributor.author | Su-Ru Lin | en |
dc.contributor.author | 林素如 | zh_TW |
dc.date.accessioned | 2021-05-20T20:17:48Z | - |
dc.date.available | 2011-09-15 | |
dc.date.available | 2021-05-20T20:17:48Z | - |
dc.date.copyright | 2009-09-15 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-01 | |
dc.identifier.citation | Ackermann, M. & Padmanabhan, R. (2001). De novo synthesis of RNA by the dengue virus RNA-dependent RNA polymerase exhibits temperature dependence at the initiation but not elongation phase. J Biol Chem 276, 39926-39937.
Acosta, E. G., Castilla, V. & Damonte, E. B. (2008). Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrin-mediated endocytosis. J Gen Virol 89, 474-484. Aleshin, A. E., Shiryaev, S. A., Strongin, A. Y. & Liddington, R. C. (2007). Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold. Protein Sci 16, 795-806. Allison, S. L., Schalich, J., Stiasny, K., Mandl, C. W., Kunz, C. & Heinz, F. X. (1995). Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69, 695-700. Allison, S. L., Stiasny, K., Stadler, K., Mandl, C. W. & Heinz, F. X. (1999). Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein E. J Virol 73, 5605-5612. Allison, S. L., Tao, Y. J., O'Riordain, G., Mandl, C. W., Harrison, S. C. & Heinz, F. X. (2003). Two distinct size classes of immature and mature subviral particles from tick-borne encephalitis virus. J Virol 77, 11357-11366. Amberg, S. M., Nestorowicz, A., McCourt, D. W. & Rice, C. M. (1994). NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol 68, 3794-3802. Arias, C. F., Preugschat, F. & Strauss, J. H. (1993). Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. Virology 193, 888-899. Balmaseda, A., Hammond, S. N., Tellez, Y., Imhoff, L., Rodriguez, Y., Saborio, S. I., Mercado, J. C., Perez, L., Videa, E., Almanza, E., Kuan, G., Reyes, M., Saenz, L., Amador, J. J. & Harris, E. (2006). High seroprevalence of antibodies against dengue virus in a prospective study of schoolchildren in Managua, Nicaragua. Trop Med Int Health 11, 935-942. Bazan, J. F. & Fletterick, R. J. (1989). Detection of a trypsin-like serine protease domain in flaviviruses and pestiviruses. Virology 171, 637-639. Benarroch, D., Egloff, M. P., Mulard, L., Guerreiro, C., Romette, J. L. & Canard, B. (2004). A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate. J Biol Chem 279, 35638-35643. Blackwell, J. L. & Brinton, M. A. (1997). Translation elongation factor-1 alpha interacts with the 3' stem-loop region of West Nile virus genomic RNA. J Virol 71, 6433-6444. Blair, P. J., Kochel, T. J., Raviprakash, K., Guevara, C., Salazar, M., Wu, S. J., Olson, J. G. & Porter, K. R. (2006). Evaluation of immunity and protective efficacy of a dengue-3 pre-membrane and envelope DNA vaccine in Aotus nancymae monkeys. Vaccine 24, 1427-1432. Brandt, W. E., Chiewslip, D., Harris, D. L. & Russell, P. K. (1970). Partial purification and characterization of a dengue virus soluble complement-fixing antigen. J Immunol 105, 1565-1568. Bressanelli, S., Stiasny, K., Allison, S. L., Stura, E. A., Duquerroy, S., Lescar, J., Heinz, F. X. & Rey, F. A. (2004). Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J 23, 728-738. Brooks, A. J., Johansson, M., John, A. V., Xu, Y., Jans, D. A. & Vasudevan, S. G. (2002). The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals. J Biol Chem 277, 36399-36407. Buckley, A., Gaidamovich, S., Turchinskaya, A. & Gould, E. A. (1992). Monoclonal antibodies identify the NS5 yellow fever virus non-structural protein in the nuclei of infected cells. J Gen Virol 73 ( Pt 5), 1125-1130. Bunning, M. L., Fox, P. E., Bowen, R. A., Komar, N., Chang, G. J., Speaker, T. J., Stephens, M. R., Nemeth, N., Panella, N. A., Langevin, S. A., Gordy, P., Teehee, M., Bright, P. R. & Turell, M. J. (2007). DNA vaccination of the American crow (Corvus brachyrhynchos) provides partial protection against lethal challenge with West Nile virus. Avian Dis 51, 573-577. Burke, D. S., Nisalak, A., Johnson, D. E. & Scott, R. M. N. (1988). A prospective study of dengue infections in Bangkok. The American journal of tropical medicine and hygiene 38, 172-180. Chambers, T. J., Grakoui, A. & Rice, C. M. (1991). Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J Virol 65, 6042-6050. Chambers, T. J., McCourt, D. W. & Rice, C. M. (1990a). Production of yellow fever virus proteins in infected cells: identification of discrete polyprotein species and analysis of cleavage kinetics using region-specific polyclonal antisera. Virology 177, 159-174. Chambers, T. J., Nestorowicz, A., Amberg, S. M. & Rice, C. M. (1993). Mutagenesis of the yellow fever virus NS2B protein: effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication. J Virol 67, 6797-6807. Chambers, T. J., Nestorowicz, A. & Rice, C. M. (1995). Mutagenesis of the yellow fever virus NS2B/3 cleavage site: determinants of cleavage site specificity and effects on polyprotein processing and viral replication. J Virol 69, 1600-1605. Chambers, T. J., Weir, R. C., Grakoui, A., McCourt, D. W., Bazan, J. F., Fletterick, R. J. & Rice, C. M. (1990b). 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. Proc Natl Acad Sci U S A 87, 8898-8902. Chang, G. J., Davis, B. S., Stringfield, C. & Lutz, C. (2007). Prospective immunization of the endangered California condors (Gymnogyps californianus) protects this species from lethal West Nile virus infection. Vaccine 25, 2325-2330. Chang, G. J., Hunt, A. R. & Davis, B. (2000). A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice. J Virol 74, 4244-4252. Chang, G. J., Hunt, A. R., Holmes, D. A., Springfield, T., Chiueh, T. S., Roehrig, J. T. & 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. Chao, D. Y., Lin, T. H., Hwang, K. P., Huang, J. H., Liu, C. C. & King, C. C. (2004). 1998 dengue hemorrhagic fever epidemic in Taiwan. Emerg Infect Dis 10, 552-554. Chen, C. & Okayama, H. (1987). High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7, 2745-2752. Chen, C. J., Kuo, M. D., Chien, L. J., Hsu, S. L., Wang, Y. M. & Lin, J. H. (1997). RNA-protein interactions: involvement of NS3, NS5, and 3' noncoding regions of Japanese encephalitis virus genomic RNA. J Virol 71, 3466-3473. Chen, S. S., Lee, S. F. & Wang, C. T. (2001). Cellular membrane-binding ability of the C-terminal cytoplasmic domain of human immunodeficiency virus type 1 envelope transmembrane protein gp41. J Virol 75, 9925-9938. Chen, S. T., Lin, Y. L., Huang, M. T., Wu, M. F., Cheng, S. C., Lei, H. Y., Lee, C. K., Chiou, T. W., Wong, C. H. & Hsieh, S. L. (2008). CLEC5A is critical for dengue-virus-induced lethal disease. Nature 453, 672-676. Chen, W. J., Wei, H. L., Hsu, E. L. & Chen, E. R. (1993). Vector competence of Aedes albopictus and Ae. aegypti (Diptera: Culicidae) to dengue 1 virus on Taiwan: development of the virus in orally and parenterally infected mosquitoes. J Med Entomol 30, 524-530. Chen, Y. C., Wang, S. Y. & 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. Chung, K. M., Liszewski, M. K., Nybakken, G., Davis, A. E., Townsend, R. R., Fremont, D. H., Atkinson, J. P. & Diamond, M. S. (2006a). West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc Natl Acad Sci U S A 103, 19111-19116. Chung, K. M., Nybakken, G. E., Thompson, B. S., Engle, M. J., Marri, A., Fremont, D. H. & Diamond, M. S. (2006b). Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms. J Virol 80, 1340-1351. Cleaves, G. R. & Dubin, D. T. (1979). Methylation status of intracellular dengue type 2 40 S RNA. Virology 96, 159-165. Cleaves, G. R., Ryan, T. E. & Schlesinger, R. W. (1981). Identification and characterization of type 2 dengue virus replicative intermediate and replicative form RNAs. Virology 111, 73-83. Clum, S., Ebner, K. E. & Padmanabhan, R. (1997). Cotranslational membrane insertion of the serine proteinase precursor NS2B-NS3(Pro) of dengue virus type 2 is required for efficient in vitro processing and is mediated through the hydrophobic regions of NS2B. J Biol Chem 272, 30715-30723. Cologna, R., Armstrong, P. M. & Rico-Hesse, R. (2005). Selection for virulent dengue viruses occurs in humans and mosquitoes. Journal of virology 79, 853-859. Crill, W. D. & 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. Cui, T., Sugrue, R. J., Xu, Q., Lee, A. K., Chan, Y. C. & Fu, J. (1998). Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding and NTPase activity regulated by the NS5 protein. Virology 246, 409-417. Davis, B. S., Chang, G. J., Cropp, B., Roehrig, J. T., Martin, D. A., Mitchell, C. J., Bowen, R. & Bunning, M. L. (2001). West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 75, 4040-4047. De Nova-Ocampo, M., Villegas-Sepulveda, N. & del Angel, R. M. (2002). Translation elongation factor-1alpha, La, and PTB interact with the 3' untranslated region of dengue 4 virus RNA. Virology 295, 337-347. De Paula, S. O., Lima, D. M., de Oliveira Franca, R. F., Gomes-Ruiz, A. C. & 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. Dokland, T., Walsh, M., Mackenzie, J. M., Khromykh, A. A., Ee, K. H. & Wang, S. (2004). West Nile virus core protein; tetramer structure and ribbon formation. Structure 12, 1157-1163. Domingo, E., Holland, J. & Ahlquist, P. (1988). RNA genetics, vol. 3, Variability of RNA genomes. Boca Raton, Fla: CRC Press. Egloff, M. P., Benarroch, D., Selisko, B., Romette, J. L. & Canard, B. (2002). An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J 21, 2757-2768. Endy, T. P., Chunsuttiwat, S., Nisalak, A., Libraty, D. H., Green, S., Rothman, A. L., Vaughn, D. W. & Ennis, F. A. (2002). Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 156, 40-51. Eram, S., Setyabudi, Y., Sadono, T. I., Sutrisno, D. S., Gubler, D. J. & Sulianti Saroso, J. (1979). Epidemic dengue hemorrhagic fever in rural Indonesia. II. Clinical studies. Am J Trop Med Hyg 28, 711-716. Falgout, B., Chanock, R. & Lai, C. J. (1989). Proper processing of dengue virus nonstructural glycoprotein NS1 requires the N-terminal hydrophobic signal sequence and the downstream nonstructural protein NS2a. J Virol 63, 1852-1860. Falgout, B. & Markoff, L. (1995). Evidence that flavivirus NS1-NS2A cleavage is mediated by a membrane-bound host protease in the endoplasmic reticulum. J Virol 69, 7232-7243. Falgout, B., Pethel, M., Zhang, Y. M. & Lai, C. J. (1991). Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J Virol 65, 2467-2475. Farci, P., Shimoda, A., Coiana, A., Diaz, G., Peddis, G., Melpolder, J. C., Strazzera, A., Chien, D. Y., Munoz, S. J., Balestrieri, A., Purcell, R. H. & Alter, H. J. (2000). The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288, 339-344. Felsenstein, J. (2005). PHYLIP (Phylogeny Inference Package) version 3.6. . Distributed by the author Department of Genome Sciences, University of Washington, Seattle. Ferlenghi, I., Clarke, M., Ruttan, T., Allison, S. L., Schalich, J., Heinz, F. X., Harrison, S. C., Rey, F. A. & Fuller, S. D. (2001). Molecular organization of a recombinant subviral particle from tick-borne encephalitis virus. Mol Cell 7, 593-602. Flamand, M., Megret, F., Mathieu, M., Lepault, J., Rey, F. A. & Deubel, V. (1999). Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion. J Virol 73, 6104-6110. Garcia-Montalvo, B. M., Medina, F. & del Angel, R. M. (2004). La protein binds to NS5 and NS3 and to the 5' and 3' ends of Dengue 4 virus RNA. Virus Res 102, 141-150. Gibbons, D. L., Vaney, M. C., Roussel, A., Vigouroux, A., Reilly, B., Lepault, J., Kielian, M. & Rey, F. A. (2004). Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus. Nature 427, 320-325. Gollins, S. W. & Porterfield, J. S. (1985). Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry. J Gen Virol 66 ( Pt 9), 1969-1982. Gollins, S. W. & Porterfield, J. S. (1986). The uncoating and infectivity of the flavivirus West Nile on interaction with cells: effects of pH and ammonium chloride. J Gen Virol 67 ( Pt 9), 1941-1950. Gorbalenya, A. E., Donchenko, A. P., Koonin, E. V. & Blinov, V. M. (1989a). N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res 17, 3889-3897. Gorbalenya, A. E., Koonin, E. V., Donchenko, A. P. & Blinov, V. M. (1989b). Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res 17, 4713-4730. Green, S. & Rothman, A. (2006). Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Current Opinion in Infectious Diseases 19, 429. 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. & Casta-Valez, A. (1991). A program for prevention and control of epidemic dengue and dengue hemorrhagic fever in Puerto Rico and the U.S. Virgin Islands. Bull Pan Am Health Organ 25, 237-247. Gubler, D. J. & Clark, G. G. (1995). Dengue/dengue hemorrhagic fever: the emergence of a global health problem. Emerg Infect Dis 1, 55-57. Gubler, D. J., Reed, D., Rosen, L. & Hitchcock Jr, J. C. (1978). Epidemiologic, clinical, and virologic observations on dengue in the Kingdom of Tonga. The American journal of tropical medicine and hygiene 27, 581. Gubler, D. J. & Rosen, L. (1976). A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts. Am J Trop Med Hyg 25, 146-150. Guyatt, K. J., Westaway, E. G. & Khromykh, A. A. (2001). Expression and purification of enzymatically active recombinant RNA-dependent RNA polymerase (NS5) of the flavivirus Kunjin. J Virol Methods 92, 37-44. Guzman, M. G. & Kouri, G. (2002). Dengue: an update. Lancet Infectious Diseases 2, 33-42. Guzman, M. G., Kouri, G. & Halstead, S. B. (2000). Do escape mutants explain rapid increases in dengue casefatality rates within epidemics? The Lancet 355, 1902-1903. Guzman, M. G., Kouri, G., Valdes, L., Bravo, J., Vazquez, S. & Halstead, S. B. (2002). Enhanced severity of secondary dengue-2 infections: death rates in 1981 and 1997 Cuban outbreaks. Revista Panamericana de Salud Publica 11, 223-227. Guzman, M. G., Kouri, G. P., Bravo, J., Soler, M., Vazquez, S. & Morier, L. (1990). Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study. The American journal of tropical medicine and hygiene 42, 179-184. Halstead, S. (1997). Epidemiology of dengue and dengue hemorrhagic fever. In Dengue and dengue hemorrhagic fever, pp. 23-44. Edited by D. Gubler & G. Kuno. Wallingford, Oxon, UK :: CAB International. Halstead, S. B. (1988). Pathogenesis of dengue: challenges to molecular biology. Science 239, 476-481. Halstead, S. B., Lan, N. T., Myint, T. T., Shwe, T. N., Nisalak, A., Kalyanarooj, S., Nimmannitya, S., Soegijanto, S., Vaughn, D. W. & Endy, T. P. (2002). Dengue hemorrhagic fever in infants: research opportunities ignored. Emerg Infect Dis 8, 1474-1479. Halstead, S. B., Nimmannitya, S. & Cohen, S. N. (1970). Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med 42, 311-328. Halstead, S. B., Nimmannitya, S. & Margiotta, M. R. (1969). Dengue and chikungunya virus infection in man in Thailand, 1962-1964. II. Observations on disease in outpatients. Am J Trop Med Hyg 18, 972-983. Halstead, S. B., Nimmannitya, S., Yamarat, C. & Russell, P. K. (1967). Hemorrhagic fever in Thailand; recent knowledge regarding etiology. Jpn J Med Sci Biol 20 Suppl, 96-103. Halstead, S. B. & O'Rourke, E. J. (1977). Antibody-enhanced dengue virus infection in primate leukocytes. Nature 265, 739-741. Harris, E., Roberts, T. G., Smith, L., Selle, J., Kramer, L. D., Valle, S., Sandoval, E. & Balmaseda, A. (1998). Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR. J Clin Microbiol 36, 2634-2639. Hayes, E. B. & Gubler, D. J. (1992). Dengue and dengue hemorrhagic fever. Pediatr Infect Dis J 11, 311-317. Holland, J. J., De La Torre, J. C. & Steinhauer, D. A. (1992). RNA virus populations as quasispecies. Curr Top Microbiol Immunol 176, 1-20. Holmes, E. C. (2003). Patterns of Intra- and Interhost Nonsynonymous Variation Reveal Strong Purifying Selection in Dengue Virus. J Virol 77, 11296-11298. Holmes, E. C. & Twiddy, S. S. (2003). The origin, emergence and evolutionary genetics of dengue virus. Infection, Genetics and Evolution 3, 19-28. Hsieh, S. C., Liu, I. J., King, C. C., Chang, G. J. & Wang, W. K. (2008). A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles. Virology 374, 338-350. Hu, H. P., Hsieh, S. C., King, C. C. & 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. Huelsenbeck, J. P. & Ronquist, F. (2001). MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17, 754-755. Hung, S. L., Lee, P. L., Chen, H. W., Chen, L. K., Kao, C. L. & King, C. C. (1999). Analysis of the steps involved in Dengue virus entry into host cells. Virology 257, 156-167. Hunt, A. R., Cropp, C. B. & 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. Innis, B. L., Thirawuth, V. & Hemachudha, C. (1989). Identification of continuous epitopes of the envelope glycoprotein of dengue type 2 virus. Am J Trop Med Hyg 40, 676-687. Irie, K., Mohan, P. M., Sasaguri, Y., Putnak, R. & Padmanabhan, R. (1989). Sequence analysis of cloned dengue virus type 2 genome (New Guinea-C strain). Gene 75, 197-211. Jan, L. R., Yang, C. S., Trent, D. W., Falgout, B. & Lai, C. J. (1995). Processing of Japanese encephalitis virus non-structural proteins: NS2B-NS3 complex and heterologous proteases. J Gen Virol 76 ( Pt 3), 573-580. Jardetzky, T. S. & Lamb, R. A. (2004). Virology: a class act. Nature 427, 307-308. Jindadamrongwech, S., Thepparit, C. & 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. Johansson, M., Brooks, A. J., Jans, D. A. & Vasudevan, S. G. (2001). A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3. J Gen Virol 82, 735-745. Jones, C. T., Ma, L., Burgner, J. W., Groesch, T. D., Post, C. B. & Kuhn, R. J. (2003). Flavivirus capsid is a dimeric alpha-helical protein. J Virol 77, 7143-7149. Kapoor, M., Zhang, L., Ramachandra, M., Kusukawa, J., Ebner, K. E. & Padmanabhan, R. (1995). Association between NS3 and NS5 proteins of dengue virus type 2 in the putative RNA replicase is linked to differential phosphorylation of NS5. J Biol Chem 270, 19100-19106. Kiernan, R., Ono, A. & Freed, E. (1999). Reversion of a human immunodeficiency virus type 1 matrix mutation affecting Gag membrane binding, endogenous reverse transcriptase activity, and virus infectivity. Journal of virology 73, 4728-4737. King, C., Wu, Y., Chao, D., Lin, T., Chow, L., Wang, H., Ku, C., Kao, C., Hwang, K., Lam, S. & Gubler, D. (2000). Major epidemics of dengue in Taiwan in 1991-2000: related to intensive virus activities in Asia. Geneva, Switzerland: World Health Organization. Kliks, S. C., Nimmanitya, S., Nisalak, A. & Burke, D. S. (1988). Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38, 411-419. Klungthong, C., Zhang, C., Mammen, M. P., Ubol, S. & Holmes, E. C. (2004). The molecular epidemiology of dengue virus serotype 4 in Bangkok, Thailand. Virology 329, 168-179. Kochel, T. J., Raviprakash, K., Hayes, C. G., Watts, D. M., Russell, K. L., Gozalo, A. S., Phillips, I. A., Ewing, D. F., Murphy, G. S. & Porter, K. R. (2000). A dengue virus serotype-1 DNA vaccine induces virus neutralizing antibodies and provides protection from viral challenge in Aotus monkeys. Vaccine 18, 3166-3173. Kofler, R. M., Heinz, F. X. & Mandl, C. W. (2002). Capsid protein C of tick-borne encephalitis virus tolerates large internal deletions and is a favorable target for attenuation of virulence. J Virol 76, 3534-3543. Kofler, R. M., Leitner, A., O'Riordain, G., Heinz, F. X. & Mandl, C. W. (2003). Spontaneous mutations restore the viability of tick-borne encephalitis virus mutants with large deletions in protein C. J Virol 77, 443-451. Konishi, E. & Mason, P. W. (1993). Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol 67, 1672-1675. Konishi, E., Yamaoka, M., Kurane, I. & Mason, P. W. (2000). A DNA vaccine expressing dengue type 2 virus premembrane and envelope genes induces neutralizing antibody and memory B cells in mice. Vaccine 18, 1133-1139. Koonin, E. V. (1993). Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus. J Gen Virol 74 ( Pt 4), 733-740. Koonin, E. V. & Dolja, V. V. (1993). Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. Crit Rev Biochem Mol Biol 28, 375-430. Kuberski, T. T. & Rosen, L. (1977). A simple technique for the detection of dengue antigen in mosquitoes by immunofluorescence. Am J Trop Med Hyg 26, 533-537. 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., Baker, T. S. & Strauss, J. H. (2002). Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717-725. Kummerer, B. M. & Rice, C. M. (2002). Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J Virol 76, 4773-4784. Kuno, G. (1997). Factors influencing the transmission of dengue viruses. In Dengue and dengue hemorrhagic fever pp. 61-88. Edited by D. Gubler & G. Kuno. Wallingford, Oxon, UK: CAB International. Kuno, G., Chang, G. J., Tsuchiya, K. R., Karabatsos, N. & Cropp, C. B. (1998). Phylogeny of the genus Flavivirus. J Virol 72, 73-83. Lanciotti, R. S., Calisher, C. H., Gubler, D. J., Chang, G. J. & Vorndam, A. V. (1992). Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. Journal of Clinical Microbiology 30, 545-551. Lanciotti, R. S., Lewis, J. G., Gubler, D. J. & Trent, D. W. (1994). Molecular evolution and epidemiology of dengue-3 viruses. J Gen Virol 75 ( Pt 1), 65-75. Lee, I. K., Liu, J. W. & Yang, K. D. (2005). Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. The American journal of tropical medicine and hygiene 72, 221-226. Leitmeyer, K. C., Vaughn, D. W., Watts, D. M., Salas, R., Villalobos, I., Ramos, C. & Rico-Hesse, R. (1999). Dengue virus structural differences that correlate with pathogenesis. Journal of virology 73, 4738-4747. Li, L., Lok, S. M., Yu, I. M., Zhang, Y., Kuhn, R. J., Chen, J. & Rossmann, M. G. (2008). The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science 319, 1830-1834. Lin, Y. J. & Wu, S. C. (2005). Histidine at residue 99 and the transmembrane region of the precursor membrane prM protein are important for the prM-E heterodimeric complex formation of Japanese encephalitis virus. J Virol 79, 8535-8544. Lindenbach, B. D. & Rice, C. M. (1997). trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol 71, 9608-9617. Lindenbach, B. D. & Rice, C. M. (1999). Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol 73, 4611-4621. Lindenbach, B. D., Thiel, H.-J. & Rice, C. M. (2007). Flaviviridae: the viruses and their replication. In Fields' virology, 5 edn, pp. 1103-1113. Edited by D. M. Knipe & P. M. Howley. Philadelphia :: Wolters Kluwer Health/Lippincott Williams & Wilkins. Liu, W. J., Chen, H. B. & Khromykh, A. A. (2003). Molecular and functional analyses of Kunjin virus infectious cDNA clones demonstrate the essential roles for NS2A in virus assembly and for a nonconservative residue in NS3 in RNA replication. J Virol 77, 7804-7813. Liu, W. J., Chen, H. B., Wang, X. J., Huang, H. & Khromykh, A. A. (2004). Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription. J Virol 78, 12225-12235. Liu, W. J., Wang, X. J., Clark, D. C., Lobigs, M., Hall, R. A. & Khromykh, A. A. (2006). A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice. J Virol 80, 2396-2404. Lobigs, M. (1993). Flavivirus premembrane protein cleavage and spike heterodimer secretion require the function of the viral proteinase NS3. Proc Natl Acad Sci U S A 90, 6218-6222. Lorenz, I. C., Allison, S. L., Heinz, F. X. & 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. Lorenz, I. C., Kartenbeck, J., Mezzacasa, A., Allison, S. L., Heinz, F. X. & Helenius, A. (2003). Intracellular assembly and secretion of recombinant subviral particles from tick-borne encephalitis virus. J Virol 77, 4370-4382. Lowry, O., Rosebrough, N., Farr, A. & Randall, R. (1951). Protein measurement with the Folin phenol reagent. Journal of biological chemistry 193, 265-275. Lozach, P. Y., Burleigh, L., Staropoli, I., Navarro-Sanchez, E., Harriague, J., Virelizier, J. L., Rey, F. A., Despres, P., Arenzana-Seisdedos, F. & 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. Lu, M., Funsch, B., Wiese, M. & Roggendorf, M. (1995). Analysis of hepatitis C virus quasispecies populations by temperature gradient gel electrophoresis. J Gen Virol 76 ( Pt 4), 881-887. Luo, D., Xu, T., Hunke, C., Gruber, G., Vasudevan, S. G. & Lescar, J. (2008). Crystal structure of the NS3 protease-helicase from dengue virus. J Virol 82, 173-183. Ma, L., Jones, C. T., Groesch, T. D., Kuhn, R. J. & Post, C. B. (2004). Solution structure of dengue virus capsid protein reveals another fold. Proc Natl Acad Sci U S A 101, 3414-3419. Mackenzie, J. M., Jones, M. K. & Young, P. R. (1996). Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220, 232-240. Mackenzie, J. M., Khromykh, A. A., Jones, M. K. & Westaway, E. G. (1998). Subcellular localization and some biochemical properties of the flavivirus Kunjin nonstructural proteins NS2A and NS4A. Virology 245, 203-215. Mackenzie, J. M. & Westaway, E. G. (2001). Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75, 10787-10799. Malet, H., Egloff, M. P., Selisko, B., Butcher, R. E., Wright, P. J., Roberts, M., Gruez, A., Sulzenbacher, G., Vonrhein, C., Bricogne, G., Mackenzie, J. M., Khromykh, A. A., Davidson, A. D. & Canard, B. (2007). Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5. J Biol Chem 282, 10678-10689. Mandl, C. W., Heinz, F. X. & Kunz, C. (1988). Sequence of the structural proteins of tick-borne encephalitis virus (western subtype) and comparative analysis with other flaviviruses. Virology 166, 197-205. Mangada, M. N. M. & Igarashi, A. (1998). Molecular andin VitroAnalysis of Eight Dengue Type 2 Viruses Isolated from Patients Exhibiting Different Disease Severities. Virology 244, 458-466. Martell, M., Esteban, J. I., Quer, J., Genesca, J., Weiner, A., Esteban, R., Guardia, J. & Gomez, J. (1992). Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol 66, 3225-3229. Martin, J. E., Pierson, T. C., Hubka, S., Rucker, S., Gordon, I. J., Enama, M. E., Andrews, C. A., Xu, Q., Davis, B. S., Nason, M., Fay, M., Koup, R. A., Roederer, M., Bailer, R. T., Gomez, P. L., Mascola, J. R., Chang, G. J., Nabel, G. J. & Graham, B. S. (2007). A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis 196, 1732-1740. Mason, P. W. (1989). Maturation of Japanese encephalitis virus glycoproteins produced by infected mammalian and mosquito cells. Virology 169, 354-364. Matusan, A. E., Pryor, M. J., Davidson, A. D. & Wright, P. J. (2001). Mutagenesis of the Dengue virus type 2 NS3 protein within and outside helicase motifs: effects on enzyme activity and virus replication. J Virol 75, 9633-9643. Meyerhans, A., Cheynier, R., Albert, J., Seth, M., Kwok, S., Sninsky, J., Morfeldt-Manson, L., Asjo, B. & Wain-Hobson, S. (1989). Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell 58, 901-910. Miller, S., Kastner, S., Krijnse-Locker, J., Buhler, S. & Bartenschlager, R. (2007). The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alter | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9329 | - |
dc.description.abstract | 登革病毒為黃病毒科,黃病毒屬之一員,有血清型1∼4型。登革病毒感染為在熱帶及亞熱帶地區流行的蟲媒病毒疾病之首位,可引起自限性的登革熱以及顏重致死的登革出血熱�登革休克症候群。官方估計全球每年約有5千萬∼1億人口感染登革病毒,其中有25萬∼50萬是登革出血熱病例。登革病毒之基因體為一正向、單股之核醣核酸,可在轉譯成3個結構性蛋白質,包含殼蛋白質、前驅膜蛋白質、外套膜蛋白質,以及7個非結構性蛋白質,包含非結構性蛋白質1、2A、2B、3、4A、4B、5。
目前已有許多致力於了解登革病毒感染及其致病機轉之臨床與流行病學方面的研究工作正在進行中,但對於登革病毒的傳播及複製仍有許多問題尚待解決。登革病毒的外套膜蛋白質是其細胞向性與病毒毒力之主要決定蛋白質,而且此蛋白質在登革病毒生活史中扮演許多重要的角色。因此本研究之整體目標為探就外套膜蛋白質於登革病毒傳播與複製時之功能。登革病毒可以在埃及斑蚊及宿主間交替複製。有研究報告指出登革病毒在被感染個體中以類種的形式存在,但其在病媒蚊體內之序列變異程度以及其類種結構在病媒蚊與人類宿主間傳播時之變化目前則未明。最近有流行病學研究報告指出登革出血熱的病例數在登革病毒流行的晚期有逐漸增多的趨勢,顯示登革病毒在同次流行中持續演化,然而其毒力決定區及其與疾病越趨嚴重的演化關係則尚缺定論。有研究指出在細胞中一起表現外套膜蛋白質與前驅膜蛋白質可以產生類病毒顆粒,其結構與抗原性質與具有感染力的病毒顆粒十分相似。外套膜蛋白質由N端外區(具有395個胺基酸)及C端柄與嵌入區(具有100個胺基酸)組成。由蜱媒介性腦炎病毒的外套膜蛋白質之連續截斷蛋白質研究顯示其柄區域對於類病毒顆粒之形成極為重要,然而影響此功能之重要殘基為何則尚待研究。 本研究的第一個目標為研究登革病毒在病媒蚊體內之序列變異程度與在傳播時其類種結構之變化。我們分析來自同一次登革病毒流行時,取樣自自然感染的病媒蚊及八位登革病人血漿中的登革病毒血清型第三型之核酸序列。以外套膜基因為例,在登革病毒病媒蚊體內的平均歧異度為(0.21%)較在登革病人體內(0.38%)為低。分析殼蛋白基因也有類似的分析結果,病媒蚊體內的殼蛋白基因平均歧異度為0.09%,低於在登革病人體內的0.23%。我們更進一步分析五隻用實驗感染登革病毒的蚊子體內的登革病毒外套膜基因(平均歧異度為0.09%)與殼蛋白基因(平均歧異度為0.1%)證實這項推論。我們的實驗結果顯示登革病毒在病媒蚊體內之序列變異程度普遍低於在病人體內。同時我們也以在病媒蚊與病人體內的登革病毒外套膜基因變異度分析其類種結構,結果顯示二者的主要變種序列相同,於是我們推測這個主要變種在病媒蚊與病人之間傳播。總而言之,我們的實驗結果支持「病媒蚊對於登革病毒演化之保守性有所貢獻」的假說,也就是登革病毒在病媒蚊體內保持序列較為相近的病毒族群及以主要變種傳播。 本研究的第二個目標為探討登革病毒毒力決定區及其與疾病越趨嚴重的演化關係。我們分析了來自2001至2002年台灣南部連續的兩次登革病毒血清型第二型流行時所採樣的31位病人(14個登革熱病例及17個登革出血熱病例)血漿中的登革病毒血清型第二型序列。結果顯示有五個分別在外套膜基因、非結構性蛋白基因1、4A、5的核酸變異。此結果與1997年在古巴流行的登革病毒血清型第二型之分析報告並無重複,所以我們推測與嚴重流行相關之病毒毒力決定區與造成流行之基因型有關。與其他研究兩次間隔數年的登革病毒流行之譜系交替的報告相較之下,我們的分析結果顯示2002年的高雄登革病毒來自於2001年的小部分病毒變種,而這中間只經過不到6個月的時間。我們的發現可能也代表著一種登革病毒在流行期之間的演化機制。 本研究的第三個目標為在一個可以同時表現登革病毒血清型第四型外套膜蛋白質與膜蛋白質前驅蛋白質的質體系統中,以點突變的方法尋找外套膜蛋白質柄區域中對於類病毒顆粒形成之重要殘基。我們發現位於外套膜蛋白質柄區域的第一螺旋區域(H1)之胺基酸殘基位置398、401、405、408,第二螺旋區域(H2)之胺基酸殘基位置429、436、439、446以及其間胺基酸殘基位置422若以脯胺酸取代原本胺基酸會造成類病毒顆粒之產量減少。共免疫沉澱實驗結果顯示位於H1之點突變影響外套膜蛋白質與膜蛋白質前驅蛋白質之交互作用,位於H2之點突變則未然。脂質膜結合能力實驗結果則顯示帶有造成降低類病毒顆粒形成的H2之點突變亦損害其與脂質膜之結合能力,而帶有造成降低類病毒顆粒形成的H1之點突變則未然。綜合以上實驗結果,我們發現外套膜蛋白質柄區域之H1殘基藉參與其與膜蛋白質前驅蛋白質間之交互作用而影響類病毒顆粒之形成,而H2則因具有與脂質膜結合之能力而影響類病毒顆粒之形成。 總而言之,在本研究中顯示登革病毒在病媒蚊體內以類種的形式存在,且藉著在病媒蚊體內中相似度較高的病毒族群維持其演化上的保守性,此外我們也發現了登革病毒以主要變種傳播。同時在本研究中亦藉著大量且持續的外套膜蛋白基因以及基因體全長之序列分析釐清登革病毒從一個只有少數嚴重病例的流行到一個越來越多嚴重病例的流行是如何演化。本研究中亦更進一步探討外套膜蛋白質之柄區域如何參與類病毒顆粒之形成與其在登革病毒生活史中病毒組裝的步驟之可能功能。推而廣之,本研究提供登革病毒傳播與複製之更深入的了解以及預防與控治登革病毒之新策略。 | zh_TW |
dc.description.abstract | Dengue virus (DENV) belongs to the genus flavivirus in the family flavivirus. There are four serotypes of DENV (DENV1 to 4), which are the leading cause of the arboviral diseases in the tropical and subtropical areas, including a self-limiting disease, dengue fever (DF) and a severe and life-threatening disease, dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). It has been estimated that approximately 50-100 million of DENV infection and 250-500 thousands cases of DHF occur annually throughout the world. DENV contains a positive-sense single stranded RNA genome, which encodes three structural proteins, including capsid (C), precursor membrane (PrM) and envelope (E) at the N-terminus, and seven nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5, at the C-terminus.
While substantial efforts have been made to study the clinical and epidemiological aspects of dengue disease and pathogenesis, several fundamental questions of the transmission and replication of DENV remain unclear. The E gene of DENV is the major determinant of tropism and virulence, and is known to play important roles in the life cycles of DENV. The overall objective of this study is to focus on the E gene and investigate its roles in some poorly understood areas in the DENV transmission and replication. DENV replicates alternately in the mosquito vectors and human hosts. It has been reported that DENV is present as quasispecies in plasma of infected individuals. However, the extent of sequence variation of DENV in the mosquito vector and the quasispecies structure changes during transmission between human and mosquitoes remain unknown. Several epidemiological studies have reported recently that the proportion of severe cases, DHF, to total cases increases toward the end of an outbreak, suggesting DENV evolves during the same outbreak. However, the viral determinants and evolution linked to outbreak with increased severity remain unclear. Co-expression of PrM and E proteins is sufficient to produce virus-like particles (VLPs), which structurally and antigenically similar to infectious particles. The E protein contains 395 amino acids at the N-terminal ectodomain and 100 amino acids at its C-terminus, which consists of the stem and anchor regions. Deletional study of the E protein of the tick-borne encephalitis virus (TBEV) suggested the importance of the stem region in the formation of VLPs, however, the critical residues involved remain unknown. In the first specific aim, we studied the extent of sequences variation of DENV in the mosquitoes and the changes of quasispecies during transmission by examining DENV3 sequences in naturally infected mosquitoes in comparison with those in eight patients from the same outbreak. For the E gene, the mean diversity in naturally infected mosquitoes was 0.21%, lower than that in patients (0.38%). Similarly, the mean diversity of C gene in naturally infected mosquitoes was 0.09%, lower than 0.23% in patients. This was further verified with five experimentally infected mosquitoes (mean diversity, 0.09 and 0.10% for the E and C genes, respectively). Our findings suggested that the extent of sequence variation in the mosquitoes was generally lower than that in the patients. Examination of the quasispecies structures of the DENV3 E sequences in the mosquitoes and patients revealed that the sequences of the major variants were the same, suggesting that the major variant was transmitted. These findings support our hypothesis that mosquitoes contribute to the evolutionary conservation of dengue virus by maintaining a more homogenous viral population and a dominant variant during transmission. In the second specific aim, we investigated viral determinants and evolution linked to outbreak with increased severity by examining DENV2 sequences from plasma of 31 patients (14 DF, 17 DHF) continuously during two consecutive DENV2 outbreaks in southern Taiwan in 2001-2002, in which both the total cases and proportion of DHF cases increased. Analysis of E gene and full-genome sequences between viruses of the two outbreaks revealed 5 nucleotide changes in E, NS1, NS4A, and NS5 genes. None was identical to those reported in the DENV2 outbreak in Cuba in 1997, suggesting viral determinants linked to severe outbreak were genotype dependent. Compared with previous reports of lineage turnover years apart, our findings that the 2002 viruses descended from a minor variant of the 2001 viruses in less than 6 months were novel, and may represent a mechanism of evolution of DENV from one outbreak to another. In the third specific aim, we investigated critical residues in the stem region of E protein involved in the formation of VLPs by employing site-directed muatgenesis in the context of DENV4 PrM/E expression construct. We found that proline substitutions introduced to residues 398, 401, 405, and 408 within the first helix (H1) of the stem, residues 429, 436, 439, and 446 within the second helix (H2) of the stem, and residue 422 between H1 and H2 impaired the production of VLPs. Co-immunoprecipitation experiment revealed that mutants in the H1 affected the PrM-E interaction, whereas mutants in the H2 did not. Membrane binding assay of chimeric β-gal constructs containing the stem or mutants suggested while the H1mutants did not affect the ability of the stem to bind membrane, the H2 mutants that impaired VLP production affected such membrane-binding ability. Taken together, our findings suggest that the H1 residues of the stem region are involved in the production of VLPs by participating in the interaction with PrM protein, whereas the H2 residues are involved in the production of VLPs by contributing to the membrane association of the stem region. In summary, we showed that DENV exists as quasispecies in the mosquito vectors, and they contribute to the evolutionary conservation of DENV by maintaining a more homogenous viral population and a dominant variant during transmission. By extensive and continuous sequencing analysis of the E gene as well as full-genome, we demonstrated how DENV evolved from an outbreak with fewer severe cases to an outbreak with more severe cases. Moreover, we showed that how the stem region of DENV E protein is involved in the VLP production and presumably the assembly of DENV replication cycle. Information derived from this study would provide new insights into our understanding of the transmission and replication of DENV, as well as strategies for prevention and control of dengue diseases. | en |
dc.description.provenance | Made available in DSpace on 2021-05-20T20:17:48Z (GMT). No. of bitstreams: 1 ntu-98-D92445006-1.pdf: 1349770 bytes, checksum: 07c6126016384e4f9eff7e3d2b7c6eee (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 口試委員會審定書 1
致謝 II 摘要 III ABSTRACT VI CHAPTER 1 INTRODUCTION 1 1.1 THE IMPORTANCE OF STUDYING DENGUE VIRUS 1 1.2 CLINICAL MANIFESTATIONS AND PATHOGENESIS OF DENV INFECTION 2 1.3 TRANSMISSION CYCLES OF DENV 6 1.4 STRUCTURE AND PHYSICAL PROPERTIES OF DENV VIRION 7 1.5 GENOME ORGANIZATION AND VIRAL PROTEINS 8 1.6 REPLICATION CYCLE OF DENV AND FORMATION OF VIRUS-LIKE PARTICLES 20 1.7 SPECIFIC AIMS 24 CHAPTER 2 MATERIALS AND METHODS 29 2.1 STUDY PARTICIPANTS AND SAMPLES 29 2.2 VIRAL RNA EXTRACTION FROM PATIENTS AND MOSQUITOES 30 2.3 REVERSE TRANSCRIPTION, POLYMERASE CHAIN REACTION, AND SEQUENCING 31 2.4 CELLS AND ANTIBODIES 33 2.5 CONSTRUCTS AND PCR MUTAGENESIS 34 2.6 TRANSFECTION AND COLLECTION OF VLPS 35 2.7 WESTERN BLOT ANALYSIS 36 2.8 RADIOIMMUNOPRECIPITATION 37 2.9 MEMBRANE FLOTATION ASSAY 38 2.10 SUBCELLULAR FRACTIONATION ASSAY 40 CHAPTER 3 RESULTS 41 3.1 SEQUENCE VARIATION OF DENGUE TYPE 3 VIRUS IN NATURALLY INFECTED MOSQUITOES AND HUMAN HOSTS 41 3.2 EVOLUTION OF DENGUE VIRUS TYPE 2 DURING TWO CONSECUTIVE OUTBREAKS IN SOUTHERN TAIWAN IN 2001-2002 46 3.3 THE INVOLVEMENT OF THE STEM REGION OF DENV E PROTEIN ON PARTICLE FORMATION 51 CHAPTER 4 DISCUSSION 56 4.1 SEQUENCE VARIATION OF DENV3 VIRUS IN MOSQUITOES AND HUMAN HOSTS 56 4.2 SEQUENCE SIGNATURES CORRELATED WITH DISEASE SEVERITY 60 4.3 THE FUNCTION OF THE STEM REGION OF E PROTEIN 65 REFERENCES 94 | |
dc.language.iso | en | |
dc.title | 登革病毒外套膜蛋白質基因之研究:蚊媒與宿主之序列變異及形成病毒顆粒之功能 | zh_TW |
dc.title | Study of the Envelope Gene of Dengue Virus: Sequence Variation in Mosquito and Human Host and Functional Role in Particle Formation | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 董馨蓮(Shin-Lian Doong),張淑媛(Sui-Yuan Chang),王錦鈿(Chin-Tien Wang),陳維鈞(Wei-June Chen) | |
dc.subject.keyword | 登革病毒,序列變異,病毒演化,外套膜蛋白質,類病毒顆粒, | zh_TW |
dc.subject.keyword | dengue virus,sequence variation,virus evolution,envelope protein,virus like particle, | en |
dc.relation.page | 120 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2009-07-01 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-98-1.pdf | 1.32 MB | Adobe PDF | 檢視/開啟 |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。