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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 伍安怡 | |
| dc.contributor.author | Jui-Min Sung | en |
| dc.contributor.author | 宋瑞敏 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:12:33Z | - |
| dc.date.available | 2015-03-04 | |
| dc.date.copyright | 2013-03-04 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-02-18 | |
| dc.identifier.citation | Abougergi, M.S., Gidner, S.J., Spady, D.K., Miller, B.C., and Thiele, D.L. (2005). Fas and TNFR1, but not cytolytic granule-dependent mechanisms, mediate clearance of murine liver adenoviral infection. Hepatology 41, 97-105.
Ackermann, M., and 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. Aguirre, S., Maestre, A.M., Pagni, S., Patel, J.R., Savage, T., Gutman, D., Maringer, K., Bernal-Rubio, D., Shabman, R.S., Simon, V., et al. (2012). DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING. PLoS Pathog 8, e1002934. An, J., Kimura-Kuroda, J., Hirabayashi, Y., and Yasui, K. (1999). Development of a novel mouse model for dengue virus infection. Virology 263, 70-77. Andrews, B.S., Eisenberg, R.A., Theofilopoulos, A.N., Izui, S., Wilson, C.B., McConahey, P.J., Murphy, E.D., Roths, J.B., and Dixon, F.J. (1978). Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148, 1198-1215. Appanna, R., Huat, T.L., See, L.L., Tan, P.L., Vadivelu, J., and Devi, S. (2007). Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia. Clin Vaccine Immunol 14, 969-977. Ashour, J., Morrison, J., Laurent-Rolle, M., Belicha-Villanueva, A., Plumlee, C.R., Bernal-Rubio, D., Williams, K.L., Harris, E., Fernandez-Sesma, A., Schindler, C., and Garcia-Sastre, A. (2010). Mouse STAT2 restricts early dengue virus replication. Cell Host Microbe 8, 410-421. Avirutnan, P., Zhang, L., Punyadee, N., Manuyakorn, A., Puttikhunt, C., Kasinrerk, W., Malasit, P., Atkinson, J.P., and Diamond, M.S. (2007). Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E. PLoS Pathog 3, e183. Bach, N., Thung, S.N., and Schaffner, F. (1992). The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 15. Barbier, L., Tay, S.S., McGuffog, C., Triccas, J.A., McCaughan, G.W., Bowen, D.G., and Bertolino, P. (2012). Two lymph nodes draining the mouse liver are the preferential site of DC migration and T cell activation. J Hepatol 57, 352-358. Barth, O.M., Barreto, D.F., Paes, M.V., Takiya, C.M., Pinhao, A.T., and Schatzmayr, H.G. (2006). Morphological studies in a model for dengue-2 virus infection in mice. Mem Inst Oswaldo Cruz 101, 905-915. Bashyam, H.S., Green, S., and Rothman, A.L. (2006). Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes. J Immunol 176, 2817-2824. Beatty, M.E., Beutels, P., Meltzer, M.I., Shepard, D.S., Hombach, J., Hutubessy, R., Dessis, D., Coudeville, L., Dervaux, B., Wichmann, O., et al. (2011). Health economics of dengue: a systematic literature review and expert panel's assessment. Am J Trop Med Hyg 84, 473-488. Beaumier, C.M., Jaiswal, S., West, K.Y., Friberg, H., Mathew, A., and Rothman, A.L. (2010). Differential in vivo clearance and response to secondary heterologous infections by H2(b)-restricted dengue virus-specific CD8+ T cells. Viral Immunol 23, 477-485. Bendelac, A., Killeen, N., Littman, D.R., and Schwartz, R.H. (1994). A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263, 1774-1778. Bente, D.A., Melkus, M.W., Garcia, J.V., and Rico-Hesse, R. (2005). Dengue fever in humanized NOD/SCID mice. J Virol 79, 13797-13799. Bereczky, S., Lindegren, G., Karlberg, H., Akerstrom, S., Klingstrom, J., and Mirazimi, A. (2010). Crimean-Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout mice. J Gen Virol 91, 1473-1477. Blaney, J.E., Jr., Johnson, D.H., Manipon, G.G., Firestone, C.Y., Hanson, C.T., Murphy, B.R., and Whitehead, S.S. (2002). Genetic basis of attenuation of dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells. Virology 300, 125-139. Brinkworth, R.I., Fairlie, D.P., Leung, D., and Young, P.R. (1999). Homology model of the dengue 2 virus NS3 protease: putative interactions with both substrate and NS2B cofactor. J Gen Virol 80 ( Pt 5), 1167-1177. Carnaud, C., Lee, D., Donnars, O., Park, S.H., Beavis, A., Koezuka, Y., and Bendelac, A. (1999). Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163, 4647-4650. Caronia, S., McGarvey, M.J., Goldin, R.D., and Foster, G.R. (2004). Negative correlation between intrahepatic expression of hepatitis C antigens and apoptosis despite high-level expression of Fas and HLA antigens. J Viral Hepat 11, 511-518. Chen, H.C., Lai, S.Y., Sung, J.M., Lee, S.H., Lin, Y.C., Wang, W.K., Chen, Y.C., Kao, C.L., King, C.C., and Wu-Hsieh, B.A. (2004). Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus. J Med Virol 73, 419-431. Chen, J.P., Lu, H.L., Lai, S.L., Campanella, G.S., Sung, J.M., Lu, M.Y., Wu-Hsieh, B.A., Lin, Y.L., Lane, T.E., Luster, A.D., and Liao, F. (2006). Dengue virus induces expression of CXC chemokine ligand 10/IFN-gamma-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate. J Immunol 177, 3185-3192. Colpitts, T.M., Barthel, S., Wang, P., and Fikrig, E. (2011). Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells. PLoS One 6, e24365. Couvelard, A., Marianneau, P., Bedel, C., Drouet, M.T., Vachon, F., Henin, D., and Deubel, V. (1999). Report of a fatal case of dengue infection with hepatitis: demonstration of dengue antigens in hepatocytes and liver apoptosis. Hum Pathol 30, 1106-1110. Custer, B., Sullivan, S.D., Hazlet, T.K., Iloeje, U., Veenstra, D.L., and Kowdley, K.V. (2004). Global epidemiology of hepatitis B virus. J Clin Gastroenterol 38, S158-168. Dandri, M., and Locarnini, S. (2012). New insight in the pathobiology of hepatitis B virus infection. Gut 61 Suppl 1, i6-17. de-Oliveira-Pinto, L.M., Gandini, M., Freitas, L.P., Siqueira, M.M., Marinho, C.F., Setubal, S., Kubelka, C.F., Cruz, O.G., and Oliveira, S.A. (2012a). Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1beta and CCL2/MCP-1 in dengue fever and parvovirosis. Mem Inst Oswaldo Cruz 107, 48-56. de-Oliveira-Pinto, L.M., Marinho, C.F., Povoa, T.F., de Azeredo, E.L., de Souza, L.A., Barbosa, L.D., Motta-Castro, A.R., Alves, A.M., Avila, C.A., de Souza, L.J., et al. (2012b). Regulation of inflammatory chemokine receptors on blood T cells associated to the circulating versus liver chemokines in dengue fever. PLoS One 7, e38527. de Macedo, F.C., Nicol, A.F., Cooper, L.D., Yearsley, M., Pires, A.R., and Nuovo, G.J. (2006). Histologic, viral, and molecular correlates of dengue fever infection of the liver using highly sensitive immunohistochemistry. Diagn Mol Pathol 15, 223-228. Di Marco, V., Lo Iacono, O., Camma, C., Vaccaro, A., Giunta, M., Martorana, G., Fuschi, P., Almasio, P.L., and Craxi, A. (1995). The long-term course of chronic hepatitis B. Hepatology 30, 257-264. Disson, O., Haouzi, D., Desagher, S., Loesch, K., Hahne, M., Kremer, E.J., Jacquet, C., Lemon, S.M., Hibner, U., and Lerat, H. (2004). Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology 126, 859-872. Duangchinda, T., Dejnirattisai, W., Vasanawathana, S., Limpitikul, W., Tangthawornchaikul, N., Malasit, P., Mongkolsapaya, J., and Screaton, G. (2010). Immunodominant T-cell responses to dengue virus NS3 are associated with DHF. Proc Natl Acad Sci U S A 107, 16922-16927. Eberl, G., and MacDonald, H.R. (2000). Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 30, 985-992. Ehrlich, S., Infante-Duarte, C., Seeger, B., and Zipp, F. (2003). Regulation of soluble and surface-bound TRAIL in human T cells, B cells, and monocytes. Cytokine 24, 244-253. Franca, R.F., Zucoloto, S., and da Fonseca, B.A. (2010). A BALB/c mouse model shows that liver involvement in dengue disease is immune-mediated. Exp Mol Pathol 89, 321-326. Gagnon, S.J., Zeng, W., Kurane, I., and Ennis, F.A. (1996). Identification of two epitopes on the dengue 4 virus capsid protein recognized by a serotype-specific and a panel of serotype-cross-reactive human CD4+ cytotoxic T-lymphocyte clones. J Virol 70, 141-147. Gale, M.J., Jr., Korth, M.J., and Katze, M.G. (1998). Repression of the PKR protein kinase by the hepatitis C virus NS5A protein: a potential mechanism of interferon resistance. Clin Diagn Virol 10, 157-162. Gale, M.J., Jr., Korth, M.J., Tang, N.M., Tan, S.L., Hopkins, D.A., Dever, T.E., Polyak, S.J., Gretch, D.R., and Katze, M.G. (1997). Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 230, 217-227. Green, S., Pichyangkul, S., Vaughn, D.W., Kalayanarooj, S., Nimmannitya, S., Nisalak, A., Kurane, I., Rothman, A.L., and Ennis, F.A. (1999a). Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever. J Infect Dis 180, 1429-1435. Green, S., Vaughn, D.W., Kalayanarooj, S., Nimmannitya, S., Suntayakorn, S., Nisalak, A., Lew, R., Innis, B.L., Kurane, I., Rothman, A.L., and Ennis, F.A. (1999b). Early immune activation in acute dengue illness is related to development of plasma leakage and disease severity. J Infect Dis 179, 755-762. Guabiraba, R., Marques, R.E., Besnard, A.G., Fagundes, C.T., Souza, D.G., Ryffel, B., and Teixeira, M.M. (2010). Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice. PLoS One 5, e15680. Guilarde, A.O., Turchi, M.D., Siqueira, J.B., Jr., Feres, V.C., Rocha, B., Levi, J.E., Souza, V.A., Boas, L.S., Pannuti, C.S., and Martelli, C.M. (2008). Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response. J Infect Dis 197, 817-824. Haller, O., Stertz, S., and Kochs, G. (2007). The Mx GTPase family of interferon-induced antiviral proteins. Microbes Infect 9, 1636-1643. Hiramatsu, N., Hayashi, N., Katayama, K., Mochizuki, K., Kawanishi, Y., Kasahara, A., Fusamoto, H., and Kamada, T. (1994). Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C. Hepatology 19, 1354-1359. 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. Hsieh, M.F., Lai, S.L., Chen, J.P., Sung, J.M., Lin, Y.L., Wu-Hsieh, B.A., Gerard, C., Luster, A., and Liao, F. (2006). Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J Immunol 177, 1855-1863. Huang, K.J., Li, S.Y., Chen, S.C., Liu, H.S., Lin, Y.S., Yeh, T.M., Liu, C.C., and Lei, H.Y. (2000). Manifestation of thrombocytopenia in dengue-2-virus-infected mice. J Gen Virol 81, 2177-2182. Huerre, M.R., Lan, N.T., Marianneau, P., Hue, N.B., Khun, H., Hung, N.T., Khen, N.T., Drouet, M.T., Huong, V.T., Ha, D.Q., et al. (2001). Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Virchows Arch 438, 107-115. Hwang, I., Scott, J.M., Kakarla, T., Duriancik, D.M., Choi, S., Cho, C., Lee, T., Park, H., French, A.R., Beli, E., et al. (2012). Activation Mechanisms of Natural Killer Cells during Influenza Virus Infection. PLoS One 7, e51858. Imrie, A., Meeks, J., Gurary, A., Sukhbataar, M., Kitsutani, P., Effler, P., and Zhao, Z. (2007). Differential functional avidity of dengue virus-specific T-cell clones for variant peptides representing heterologous and previously encountered serotypes. J Virol 81, 10081-10091. Ito, H., Ando, K., Ishikawa, T., Nakayama, T., Taniguchi, M., Saito, K., Imawari, M., Moriwaki, H., Yokochi, T., Kakumu, S., and Seishima, M. (2008). Role of Valpha14+ NKT cells in the development of Hepatitis B virus-specific CTL: activation of Valpha14+ NKT cells promotes the breakage of CTL tolerance. Int Immunol 20, 869-879. Jaiswal, S., Pearson, T., Friberg, H., Shultz, L.D., Greiner, D.L., Rothman, A.L., and Mathew, A. (2009). Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PLoS One 4, e7251. Janssen, H.L., Higuchi, H., Abdulkarim, A., and Gores, G.J. (2003). Hepatitis B virus enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity by increasing TRAIL-R1/death receptor 4 expression. J Hepatol 39, 414-420. Jessie, K., Fong, M.Y., Devi, S., Lam, S.K., and Wong, K.T. (2004). Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization. J Infect Dis 189, 1411-1418. Johnson, A.J., and Roehrig, J.T. (1999). New mouse model for dengue virus vaccine testing. J Virol 73, 783-786. Kafrouni, M.I., Brown, G.R., and Thiele, D.L. (2001). Virally infected hepatocytes are resistant to perforin-dependent CTL effector mechanisms. J Immunol 167, 1566-1574. Kagi, D., Seiler, P., Pavlovic, J., Ledermann, B., Burki, K., Zinkernagel, R.M., and Hengartner, H. (1995). The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. Eur J Immunol 25, 3256-3262. Kakimi, K., Guidotti, L.G., Koezuka, Y., and Chisari, F.V. (2000). Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 192, 921-930. Kakimi, K., Lane, T.E., Wieland, S., Asensio, V.C., Campbell, I.L., Chisari, F.V., and Guidotti, L.G. (2001). Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes. J Exp Med 194, 1755-1766. Kalayanarooj, S., Vaughn, D.W., Nimmannitya, S., Green, S., Suntayakorn, S., Kunentrasai, N., Viramitrachai, W., Ratanachu-eke, S., Kiatpolpoj, S., Innis, B.L., et al. (1997). Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 176, 313-321. Kuo, C.H., Tai, D.I., Chang-Chien, C.S., Lan, C.K., Chiou, S.S., and Liaw, Y.F. (1992). Liver biochemical tests and dengue fever. Am J Trop Med Hyg 47, 265-270. 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. Kurane, I., Zeng, L., Brinton, M.A., and Ennis, F.A. (1998). Definition of an epitope on NS3 recognized by human CD4+ cytotoxic T lymphocyte clones cross-reactive for dengue virus types 2, 3, and 4. Virology 240, 169-174. Kuruvilla, J.G., Troyer, R.M., Devi, S., and Akkina, R. (2007). Dengue virus infection and immune response in humanized RAG2(-/-)gamma(c)(-/-) (RAG-hu) mice. Virology 369, 143-152. Kyle, J.L., Beatty, P.R., and Harris, E. (2007). Dengue virus infects macrophages and dendritic cells in a mouse model of infection. J Infect Dis 195, 1808-1817. Lee, C.K., Rao, D.T., Gertner, R., Gimeno, R., Frey, A.B., and Levy, D.E. (2000). Distinct requirements for IFNs and STAT1 in NK cell function. J Immunol 165, 3571-3577. Lee, L.K., Gan, V.C., Lee, V.J., Tan, A.S., Leo, Y.S., and Lye, D.C. (2012). Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity. PLoS Negl Trop Dis 6, e1676. Li, H., Zheng, H.W., Chen, H., Xing, Z.Z., You, H., Cong, M., and Jia, J.D. (2012). Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-beta1 over pro-inflammatory cytokines. Dig Liver Dis 44, 328-333. Li, S., Peng, L., Zhao, W., Zhong, H., Zhang, F., Yan, Z., and Cao, H. (2011). Synthetic peptides containing B- and T-cell epitope of dengue virus-2 E domain III provoked B- and T-cell responses. Vaccine 29, 3695-3702. Liang, S., Wei, H., Sun, R., and Tian, Z. (2003). IFNalpha regulates NK cell cytotoxicity through STAT1 pathway. Cytokine 23, 190-199. Liang, X., Liu, Y., Zhang, Q., Gao, L., Han, L., Ma, C., Zhang, L., Chen, Y.H., and Sun, W. (2007). Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax. J Immunol 178, 503-510. Limjindaporn, T., Netsawang, J., Noisakran, S., Thiemmeca, S., Wongwiwat, W., Sudsaward, S., Avirutnan, P., Puttikhunt, C., Kasinrerk, W., Sriburi, R., et al. (2007). Sensitization to Fas-mediated apoptosis by dengue virus capsid protein. Biochem Biophys Res Commun 362, 334-339. Lin, Y.L., Liao, C.L., Chen, L.K., Yeh, C.T., Liu, C.I., Ma, S.H., Huang, Y.Y., Huang, Y.L., Kao, C.L., and King, C.C. (1998). Study of Dengue virus infection in SCID mice engrafted with human K562 cells. J Virol 72, 9729-9737. Lin, Y.L., Liu, C.C., Chuang, J.I., Lei, H.Y., Yeh, T.M., Lin, Y.S., Huang, Y.H., and Liu, H.S. (2000a). Involvement of oxidative stress, NF-IL-6, and RANTES expression in dengue-2-virus-infected human liver cells. Virology 276, 114-126. Lin, Y.L., Liu, C.C., Lei, H.Y., Yeh, T.M., Lin, Y.S., Chen, R.M., and Liu, H.S. (2000b). Infection of five human liver cell lines by dengue-2 virus. J Med Virol 60, 425-431. Livingston-Rosanoff, D., Daley-Bauer, L.P., Garcia, A., McCormick, A.L., Huang, J., and Mocarski, E.S. (2012). Antiviral T cell response triggers cytomegalovirus hepatitis in mice. J Virol 86, 12879-12890. Lu, M.Y., and Liao, F. (2010). Interferon-stimulated gene ISG12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death. Cell Death Differ 18, 925-936. Luckey, S.W., and Petersen, D.R. (2001). Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol 71, 226-240. Magilavy, D.B., Steinberg, A.D., and Latta, S.L. (1987). High hepatic natural killer cell activity in murine lupus. J Exp Med 166, 271-276. Maini, M.K., Boni, C., Lee, C.K., Larrubia, J.R., Reignat, S., Ogg, G.S., King, A.S., Herberg, J., Gilson, R., Alisa, A., et al. (2000). The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 191, 1269-1280. Marianneau, P., Cardona, A., Edelman, L., Deubel, V., and Despres, P. (1997). Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death. J Virol 71, 3244-3249. Marianneau, P., Steffan, A.M., Royer, C., Drouet, M.T., Jaeck, D., Kirn, A., and Deubel, V. (1999). Infection of primary cultures of human Kupffer cells by Dengue virus: no viral progeny synthesis, but cytokine production is evident. J Virol 73, 5201-5206. Matsuda, T., Almasan, A., Tomita, M., Tamaki, K., Saito, M., Tadano, M., Yagita, H., Ohta, T., and Mori, N. (2005). Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand. J Gen Virol 86, 1055-1065. Mazzon, M., Jones, M., Davidson, A., Chain, B., and Jacobs, M. (2009). Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation. J Infect Dis 200, 1261-1270. Miller, S., Kastner, S., Krijnse-Locker, J., Buhler, S., and Bartenschlager, R. (2007). The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem 282, 8873-8882. Mota, J., and Rico-Hesse, R. (2009). Humanized mice show clinical signs of dengue fever according to infecting virus genotype. J Virol 83, 8638-8645. Munoz-Jordan, J.L., Laurent-Rolle, M., Ashour, J., Martinez-Sobrido, L., Ashok, M., Lipkin, W.I., and Garcia-Sastre, A. (2005). Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol 79, 8004-8013. Munoz-Jordan, J.L., Sanchez-Burgos, G.G., Laurent-Rolle, M., and Garcia-Sastre, A. (2003). Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci U S A 100, 14333-14338. Myint, K.S., Endy, T.P., Mongkolsirichaikul, D., Manomuth, C., Kalayanarooj, S., Vaughn, D.W., Nisalak, A., Green, S., Rothman, A.L., Ennis, F.A., and Libraty, D.H. (2006). Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis. J Infect Dis 194, 600-607. Nagila, A., Netsawang, J., Srisawat, C., Noisakran, S., Morchang, A., Yasamut, U., Puttikhunt, C., Kasinrerk, W., Malasit, P., Yenchitsomanus, P.T., and Limjindaporn, T. (2011). Role of CD137 signaling in dengue virus-mediated apoptosis. Biochem Biophys Res Commun 410, 428-433. Narumi, S., Yoneyama, H., Inadera, H., Nishioji, K., Itoh, Y., Okanoue, T., and Matsushima, K. (2000). TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma. Cytokine 12, 1007-1016. Nguyen, K.B., Salazar-Mather, T.P., Dalod, M.Y., Van Deusen, J.B., Wei, X.Q., Liew, F.Y., Caligiuri, M.A., Durbin, J.E., and Biron, C.A. (2002). Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol 169, 4279-4287. Ochi, M., Ohdan, H., Mitsuta, H., Onoe, T., Tokita, D., Hara, H., Ishiyama, K., Zhou, W., Tanaka, Y., and Asahara, T. (2004). Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice. Hepatology 39, 1321-1331. Ozturk, B., Kuscu, F., Tutuncu, E., Sencan, I., Gurbuz, Y., and Tuzun, H. (2009). Evaluation of the association of serum levels of hyaluronic acid, sICAM-1, sVCAM-1, and VEGF-A with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever. J Clin Virol 47, 115-119. Paes, M.V., Lenzi, H.L., Nogueira, A.C., Nuovo, G.J., Pinhao, A.T., Mota, E.M., Basilio-de-Oliveira, C.A., Schatzmayr, H., Barth, O.M., and Alves, A.M. (2009). Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice. Lab Invest 89, 1140-1151. Paes, M.V., Pinhao, A.T., Barreto, D.F., Costa, S.M., Oliveira, M.P., Nogueira, A.C., Takiya, C.M., Farias-Filho, J.C., Schatzmayr, H.G., Alves, A.M., and Barth, O.M. (2005). Liver injury and viremia in mice infected with dengue-2 virus. Virology 338, 236-246. Perez, A.B., Garcia, G., Sierra, B., Alvarez, M., Vazquez, S., Cabrera, M.V., Rodriguez, R., Rosario, D., Martinez, E., Denny, T., and Guzman, M.G. (2004). IL-10 levels in Dengue patients: some findings from the exceptional epidemiological conditions in Cuba. J Med Virol 73, 230-234. Pichyangkul, S., Endy, T.P., Kalayanarooj, S., Nisalak, A., Yongvanitchit, K., Green, S., Rothman, A.L., Ennis, F.A., and Libraty, D.H. (2003). A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity. J Immunol 171, 5571-5578. Porcelli, S.A., and Modlin, R.L. (1999). The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu Rev Immunol 17, 297-329. Prendergast, A.J., Klenerman, P., and Goulder, P.J. (2012). The impact of differential antiviral immunity in children and adults. Nat Rev Immunol 12, 636-648. Quaresma, J.A., Barros, V.L., Pagliari, C., Fernandes, E.R., Guedes, F., Takakura, C.F., Andrade, H.F., Jr., Vasconcelos, P.F., and Duarte, M.I. (2006). Revisiting the liver in human yellow fever: virus-induced apoptosis in hepatocytes associated with TGF-beta, TNF-alpha and NK cells activity. Virology 345, 22-30. Riera, L., Gariglio, M., Valente, G., Mullbacher, A., Museteanu, C., Landolfo, S., and Simon, M.M. (2000). Murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infection. Eur J Immunol 30, 1350-1355. Rodriguez-Madoz, J.R., Bernal-Rubio, D., Kaminski, D., Boyd, K., and Fernandez-Sesma, A. (2010). Dengue virus inhibits the production of type I interferon in primary human dendritic cells. J Virol 84, 4845-4850. Rollin, P.E., Bausch, D.G., and Sanchez, A. (2007). Blood chemistry measurements and D-Dimer levels associated with fatal and nonfatal outcomes in humans infected with Sudan Ebola virus. J Infect Dis 196 Suppl 2, S364-371. Rosen, L., Khin, M.M., and U, T. (1989). Recovery of virus from the liver of children with fatal dengue: reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever. Res Virol 140, 351-360. Roth, E., and Pircher, H. (2004). IFN-gamma promotes Fas ligand- and perforin-mediated liver cell destruction by cytotoxic CD8 T cells. J Immunol 172, 1588-1594. Rothman, A.L., Kurane, I., and Ennis, F.A. (1996). Multiple specificities in the murine CD4+ and CD8+ T-cell response to dengue virus. J Virol 70, 6540-6546. Ryman, K.D., Meier, K.C., Gardner, C.L., Adegboyega, P.A., and Klimstra, W.B. (2007). Non-pathogenic Sindbis virus causes hemorrhagic fever in the absence of alpha/beta and gamma interferons. Virology 368, 273-285. Sadler, A.J., and Williams, B.R. (2008). Interferon-inducible antiviral effectors. Nat Rev Immunol 8, 559-568. Salazar-Mather, T.P., Orange, J.S., and Biron, C.A. (1998). Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflammatory protein 1alpha (MIP-1alpha)-dependent pathways. J Exp Med 187, 1-14. Sangiambut, S., Keelapang, P., Aaskov, J., Puttikhunt, C., Kasinrerk, W., Malasit, P., and Sittisombut, N. (2008). Multiple regions in dengue virus capsid protein contribute to nuclear localization during virus infection. J Gen Virol 89, 1254-1264. Sass, G., Koerber, K., Bang, R., Guehring, H., and Tiegs, G. (2001). Inducible nitric oxide synthase is critical for immune-mediated liver injury in mice. J Clin Invest 107, 439-447. Sato, K., Hida, S., Takayanagi, H., Yokochi, T., Kayagaki, N., Takeda, K., Yagita, H., Okumura, K., Tanaka, N., Taniguchi, T., and Ogasawara, K. (2001). Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta. Eur J Immunol 31, 3138-3146. Scheuer, P.J., Ashrafzadeh, P., Sherlock, S., Brown, D., and Dusheiko, G.M. (1992). The pathology of hepatitis C. Hepatology 15, 567-571. Schul, W., Liu, W., Xu, H.Y., Flamand, M., and Vasudevan, S.G. (2007). A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis 195, 665-674. Seedhom, M.O., Mathurin, K.S., Kim, S.K., and Welsh, R.M. (2012). Increased protection from vaccinia virus infection in mice genetically prone to lymphoproliferative disorders. J Virol 86, 6010-6022. Shafee, N., and AbuBakar, S. (2003). Dengue virus type 2 NS3 protease and NS2B-NS3 protease precursor induce apoptosis. J Gen Virol 84, 2191-2195. Shields, P.L., Morland, C.M., Salmon, M., Qin, S., Hubscher, S.G., and Adams, D.H. (1999). Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver. J Immunol 163, 6236-6243. Shresta, S., Kyle, J.L., Robert Beatty, P., and Harris, E. (2004). Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice. Virology 319, 262-273. Shresta, S., Sharar, K.L., Prigozhin, D.M., Beatty, P.R., and Harris, E. (2006). Murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol 80, 10208-10217. Shresta, S., Sharar, K.L., Prigozhin, D.M., Snider, H.M., Beatty, P.R., and Harris, E. (2005). Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice. J Immunol 175, 3946-3954. Singh, N., Hong, S., Scherer, D.C., Serizawa, I., Burdin, N., Kronenberg, M., Koezuka, Y., and Van Kaer, L. (1999). Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J Immunol 163, 2373-2377. Souza, L.J., Alves, J.G., Nogueira, R.M., Gicovate Neto, C., Bastos, D.A., Siqueira, E.W., Souto Filho, J.T., Cezario Tde, A., Soares, C.E., and Carneiro Rda, C. (2004). Aminotransferase changes and acute hepatitis in patients with dengue fever: analysis of 1,585 cases. Braz J Infect Dis 8, 156-163. Spaulding, A.C., Kurane, I., Ennis, F.A., and Rothman, A.L. (1999). Analysis of murine CD8(+) T-cell clones specific for the Dengue virus NS3 protein: flavivirus cross-reactivity and influence of infecting serotype. J Virol 73, 398-403. Stout-Delgado, H.W., Getachew, Y., Miller, B.C., and Thiele, D.L. (2007). Intrahepatic lymphocyte expression of dipeptidyl peptidase I-processed granzyme B and perforin induces hepatocyte expression of serine proteinase inhibitor 6 (Serpinb9/SPI-6). J Immunol 179, 6561-6567. Su, A.I., Pezacki, J.P., Wodicka, L., Brideau, A.D., Supekova, L., Thimme, R., Wieland, S., Bukh, J., Purcell, R.H., Schultz, P.G., and Chisari, F.V. (2002). Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 99, 15669-15674. Su, G.L. (2002). Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 283, G256-265. Suksanpaisan, L., Cabrera-Hernandez, A., and Smith, D.R. (2007). Infection of human primary hepatocytes with dengue virus serotype 2. J Med Virol 79, 300-307. Takeda, K., Hayakawa, Y., Smyth, M.J., Kayagaki, N., Yamaguchi, N., Kakuta, S., Iwakura, Y., Yagita, H., and Okumura, K. (2001). Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 7, 94-100. Tan, B.H., Fu, J., Sugrue, R.J., Yap, E.H., Chan, Y.C., and Tan, Y.H. (1996). Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. Virology 216, 317-325. Tan, G.K., Ng, J.K., Trasti, S.L., Schul, W., Yip, G., and Alonso, S. (2010). A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice. PLoS Negl Trop Dis 4, e672. Taylor, D.R., Shi, S.T., Romano, P.R., Barber, G.N., and Lai, M.M. (1999). Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285, 107-110. Taylor, D.R., Tian, B., Romano, P.R., Hinnebusch, A.G., Lai, M.M., and Mathews, M.B. (2001). Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain. J Virol 75, 1265-1273. Theofilopoulos, A.N., Balderas, R.S., Gozes, Y., Aguado, M.T., Hang, L.M., Morrow, P.R., and Dixon, F.J. (1985). Association of lpr gene with graft-vs.-host disease-like syndrome. J Exp Med 162, 1-18. Thongtan, T., Panyim, S., and Smith, D.R. (2004). Apoptosis in dengue virus infected liver cell lines HepG2 and Hep3B. J Med Virol 72, 436-444. Tuiskunen, A., Wahlstrom, M., Bergstrom, J., Buchy, P., Leparc-Goffart, I., and Lundkvist, A. (2011). Phenotypic characterization of patient dengue virus isolates in BALB/c mice differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome. Virol J 8, 398. Umareddy, I., Chao, A., Sampath, A., Gu, F., and Vasudevan, S.G. (2006). Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. J Gen Virol 87, 2605-2614. Wack, A., Soldaini, E., Ts | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62854 | - |
| dc.description.abstract | 血液中肝臟酵素上升在登革病人中是一個普遍的現象，但造成肝損傷的病理機制尚不清楚。在此研究中，利用老鼠模式發現了登革病毒引起之肝損傷的免疫病理機制。免疫健全的C56BL/6小鼠靜脈注射感染登革病毒16681株後，可在血液中短暫的偵測到病毒，也可在肝臟中偵測到病毒表殼基因以及切割的凋亡蛋白酶3，自然殺手細胞及T細胞分別在感染後第一天及第五天浸潤至肝臟中，中和趨化素CXCL10或消除Asialo GM1表現的細胞後，肝臟酵素下降、肝臟中切割的凋亡蛋白酶3表現及TUNEL表現的細胞皆明顯減少，在NK 細胞毒殺能力缺乏的STAT1基因剃除小鼠中減少了早期的肝臟細胞死亡，此外，NK細胞引起的細胞死亡的機制中是部份依賴perforin的；CD4+ 及CD8+ T細胞在晚期浸潤至肝臟，此時肝臟內浸潤免疫細胞對登革病毒感染的標的細胞有毒殺能力，在TCRβ 基因剃除小鼠或消除CD8+ T細胞後，肝臟中切割的凋亡蛋白酶3表現及TUNEL表現的細胞皆明顯減少，從去除CD8的小鼠中取出的肝臟內浸潤免疫細胞喪失對感染標的細胞的毒殺能力。此外，肝臟內與脾臟內CD8 T細胞皆辨認登革病毒抗原決定位NS4B99-107，CD8+ T細胞引起的細胞死亡是需要細胞直接接觸的，但不經由perforin。因此，肝臟浸潤之自然殺手細胞及CD8 T細胞是造成肝損傷的原因，自然殺手細胞在感染後早期，而CD8 T細胞在晚期使肝臟細胞死亡，有毒殺能力的CD8 T細胞中包含了可辨認NS4B99-107胜肽鍵的CD8 T細胞。此研究提供了登革病人肝損傷的病理機制。 | zh_TW |
| dc.description.abstract | Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model, we uncovered the immunopathogenic mechanism in dengue virus-induced liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1+ cells reduced levels of liver enzymes, cleaved caspase 3 and TUNEL+ cells in the liver at day 1 after infection. Liver cell death is reduced in NK cell cytotoxic function-deficient STAT1 KO mice at day 1 after infection. Perforin is partially involved in NK cell-mediated liver cell death. Both CD4+ and CD8+ T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL) exhibited antigen-specific cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL+ cells were diminished in mice with TCRβ deficiency and in those depleted of CD8+ T cells, respectively, at day 5 after infection. IHLs isolated from CD8-depleting mice lost cytotoxicity against infected targets. Moreover, intrahepatic CD8+ T cells were like their splenic counterparts recognized DENV NS4B99-107 peptide. Intrahepatic CD8+ T cell-mediated DENV-induced liver cell death is cell-cell contact-dependent but perforin-independent. Together, these results show that infiltrating NK and CD8+ T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8+ T cells were for later. CD8+ T cells that recognize NS4B99-107 constitute at least one of the major intrahepatic cytotoxic CD8+ T cell populations. This study provokes the new pathogenic role in dengue virus-infected patients. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:12:33Z (GMT). No. of bitstreams: 1 ntu-102-D93449003-1.pdf: 4954914 bytes, checksum: 0fe2f0468c9c894f7dc6563b4b34a20b (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 誌謝……………………………………………………………………………... i
中文摘要………………………………………………………………………... ii Abstract………………………………………………………………………… iii 1. Introduction…………………………………………………………………... 1 1.1 Dengue Virus (DENV)……………………………………………... 1 1.1.1 Dengue Fever and Dengue Hemorrhage Fever…………………….. 1 1.1.2 Viral Structure……………………………………………………… 2 1.2 Liver Pathology in Viral Infection………………………………….. 3 1.2.1 Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection…. 3 1.2.2 DENV infection…………………………………………………….. 4 1.2.3 Intrahepatic Immune Cells in Viral Infection………………………. 5 1.2.4 Apoptosis Mechanisms of Hepatocytes in Viral Infection…………. 7 1.3 Immune Responses in DENV Infection…………………………… 9 1.3.1 Immune Activation………………………………………………… 9 1.3.2 Interferon Signaling………………………………………………… 10 1.3.3 Immune Epitopes of DENV………………………………………... 12 1.3.4 Chemokine Production……………………………………………... 13 1.4 Murine Models in DENV Infection………………………………… 14 1.4.1 Immune-compromised Mice……………………………………….. 14 1.4.2 Immune-competent Mice…………………………………………... 16 2. Materials and Methods……………………………………………………….. 18 2.1 Materials……………………………………………………………. 18 2.1.1 Cells lines, virus and mouse strains………………………………… 18 2.1.2 Antibodies- for flow cytometry and immunohistochemistry………. 19 2.1.3 Antibodies- for Western blotting…………………………………… 20 2.1.4 Antibodies- for in vivo depletion…………………………………… 20 2.1.5 Antibodies- for in vitro cell stimulation……………………………. 21 2.1.6 ELISA kits………………………………………………………….. 21 2.1.7 RT-PCR primers……………………………………………………. 21 2.1.8 Real-time PCR primers…………………………………………….. 22 2.1.9 Peptide sequences………………………………………………….. 23 2.1.10 Reagents…………………………………………………………… 23 2.2 Methods…………………………………………………………… 25 2.2.1 Virus infection……………………………………………………… 25 2.2.2 RT-PCR and real-time PCR………………………………………… 25 2.2.3 Detection of viremia………………………………………………... 25 2.2.4 ELISA………………………………………………………………. 26 2.2.5 Western blotting………………………...………………………….. 26 2.2.6 Isolation of intrahepatic leukocytes………………………………… 26 2.2.7 Immunohistochemistry and TUNEL staining………………………. 27 2.2.8 Immunofluoresence staining……………………………………….. 27 2.2.9 Antibody preparation and treatment………………………………... 27 2.2.10 Cell surface marker and intracellular cytokine staining……………. 28 2.2.11 In vitro cytotoxicity assay (LDH releasing) ……………………….. 28 2.2.12 In vitro cytotoxicity assay (CFSE labeling) ……………………….. 29 2.2.13 Peptide stimulation…………………………………………………. 29 2.2.14 Statistic analysis……………………………………………………. 29 3. Results………………………………………………………………………... 31 3.1 Animal Model to Study DENV-Induced Liver Injury……………… 31 3.2 Upregulation of CXCL10 and CCL5 after DENV Infection………. 32 3.3 DENV-Induced Intrahepatic NK Cell Infiltration Causes Liver Injury……………………………………………………………….. 33 3.4 Intrahepatic CD8+ T Cells Causes Cell Death after DENV Infection…………………………………………………………… 35 3.5 Both Intrahepatic and Splenic CD8+ T Cells Recognize NS4B99-107 Epitope……………………………………………………………… 36 3.6 Partial Dependence of Perforin Pathway in NK Cell-Mediated DENV-Induced Liver Injury……………………………………….. 37 4. Discussion…………………………………………………….. …………….. 39 4.1 The Role of Chemokines in DENV Infection 39 4.2 The Apoptosis Mechanism of Liver Cells 41 4.3 The Connection between NK Cells and CD8+ T Cells 42 4.4 Other Immune Cells in DENV Infection 43 4.5 The DENV Specific CD8+ T Cells 44 4.6 Liver Injury in Virus-Infection 47 4.7 Conclusion 48 5. References…………………………………………………………………… 50 6. Figures……………………………………………………………………….. 76 Fig 1 Transient viremia is detected in DENV-infected mice. ……………. 76 Fig 2 DENV infection causes liver cell death………………………..….. 77 Fig 3 CXCL10 and CCL5 are detected in the serum of DENV-infected mice. ……………………………………………………………….. 78 Fig 4 DENV infection induces the production of CXCL10 and CCL5 in the liver. ……………………………………………………………. 79 Fig 5 DENV-infected liver cell line produces CXCL10 and CCL5……… 81 Fig 6 DENV infection induces NK cell, CD4+ and CD8+ T cell infiltration into liver. ………………………………………………. 83 Fig 7 Neutralizing CXCL10 reduces NK cell infiltration. ………………. 84 Fig 8 Neutralizing CXCL10 reduces liver enzymes. …………………….. 85 Fig 9 Anti-AGM1 antibody treatment decreases intrahepatic NK cell infiltration. …………………………………………………………. 86 Fig 10 Depleting NK cell reduces DENV-induced liver cell death but not viral gene expression in liver at early phase of infection. ….……… 87 Fig 11 NK cell cytotoxic function is crucial to DENV-induced liver cell death in STAT1 KO mice…………………………………………... 88 Fig 12 Intrahepatic T cells are involved in DENV-induced liver cell death at later phase of infection. …………………………………………. 89 Fig 13 Intrahepatic leukocytes from DENV-infected mice are cytotoxic against DENV-infected Hepa 1-6 targets. …………………………. 90 Fig 14 Depleting intrahepatic CD4+ and CD8+ T cell does not alter viral gene expression in the liver….…………………………………… 92 Fig 15 Intrahepatic CD8+ but not CD4+ T cells cause DENV-induced liver cell death at later phase. ….………………………………………... 93 Fig 16 Splenic CD8+ T cells from DENV-infected mice recognize NS4B99-107 epitope. ………………………………………………… 94 Fig 17 Intrahepatic CD8+ T cell from DENV-infected wild type and STAT1 KO mice recognize NS4B99-107 epitope. …………………… 95 Fig 18 Injection of UV-inactivated DENV does not induce the expansion of CD8+ T cells that recognize NS4B99-107. ………………………. 96 Fig 19 Liver injury is persistent in lpr mice with or without DENV-infection……………………………………………………. 97 Fig 20 NK cell- but not T cell-mediated DENV-induced liver cell death is partially dependent on perforin..……..………………………….…. 98 Fig 21 Intrahepatic immune cells cause DENV-induced liver injury at different phases of infection. ………………………………………. 99 | |
| dc.language.iso | en | |
| dc.title | 肝臟浸潤免疫細胞造成登革病毒引起之肝臟損傷 | zh_TW |
| dc.title | Intrahepatic Infiltrating Immune Cells Cause Dengue Virus-Induced Liver Injury | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 孔祥智,張雯,廖楓,繆希椿 | |
| dc.subject.keyword | 登革病毒,肝損傷,肝臟內免疫細胞,NK細胞,CD8+ T細胞, | zh_TW |
| dc.subject.keyword | dengue virus,liver injury,intrahepatic immune cell,NK cell,CD8+ T cell, | en |
| dc.relation.page | 109 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-02-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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