| 研究生: |
劉明亮 Liu, Ming-liang |
|---|---|
| 論文名稱: |
第一型干擾素在腸病毒71型感染小鼠所扮演的角色 The Role of Type I Interferon on Enterovirus 71 Infection in Mice |
| 指導教授: |
余俊強
Yu, Chun-Keung |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 微生物及免疫學研究所 Department of Microbiology & Immunology |
| 論文出版年: | 2004 |
| 畢業學年度: | 92 |
| 語文別: | 英文 |
| 論文頁數: | 73 |
| 中文關鍵詞: | 第一型干擾素 、感染模式 、腸病毒 |
| 外文關鍵詞: | type I interferon, infection model, enterovirus |
| 相關次數: | 點閱:68 下載:1 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
第一型干擾素是一個具有抗病毒、抗細胞增生及免疫調控功能的細胞激素家族,並且在先天免疫對抗病毒增殖上扮演重要的角色。 在最近腸病毒71型臨床分離株的分子遺傳學研究中指出,有四種病毒基因型流行於東南亞與澳洲。 然而,這些研究在個別病毒基因型與腸病毒71型有關的臨床病徵的關聯性方面尚無法提供有力的證據。 另一方面,一些研究則指出某些宿主因素也許在腸病毒71型的致病過程扮演更重要的角色。 本研究的目的是要測試第一型干擾素是否在控制腸病毒71型感染這方面扮演一個重要的角色。
在腸病毒71型小鼠感染模式中,我們證明給予類固醇類藥物 dexsamethosome 的處理加重了感染小鼠的臨床症狀以及組織中病毒的數量。 另一方面,已知可以在體內引發大量第一型干擾素產生的人工合成雙股核醣核酸類似物 poly (I:C) 則能有效的保護感染小鼠對抗腸病毒71型的感染。給予 poly (I:C) 的處理提高了腸病毒71型感染小鼠的存活率並且降低其組織中病毒的數量。給予 poly (I:C) 的處理也能增加脾臟中 B220+/CD11c+ 細胞的比例以及樹突狀細胞 (dendritic cells) MHCⅡ 分子或α干擾素的表現。此外,是給予 poly (I:C) 處理而不是腸病毒71型感染在 ICR 小鼠體內造成第一型干擾素表現的增加。在其他的實驗中,我們使用對抗鼠科第一型干擾素抗體來中和腸病毒71型感染小鼠體內內生性的第一型干擾素。這樣的處理在腸病毒71型感染小鼠造成較低的存活率以及較高的組織內病毒數量。另外,在給予腸病毒71型感染小鼠第一型干擾素重組蛋白的實驗則證明了第一型干擾素在感染後早期的時間點給予方能保護小鼠對抗腸病毒71型的感染。
在體外實驗,我們發現第一型干擾素也能保護三種人類細胞 (SK-N-SH, RD, 和 Caco-2) 免於腸病毒71型感染所造成的細胞病變。基於以上實驗結果,我們相信第一型干擾素應該是影響腸病毒71型感染造成疾病進程其中一個重要的宿主因素並且立即的α干擾素療程也許可考慮為一治療方法。
Type I interferon, a family of cytokines with antiviral, antiproliferative, and immunomodulatory effects, plays a key role in innate control of virus replication. Recent molecular genetic studies of EV71 isolates indicate that four distinct viral genotypes circulated in East and Southeast Asia and Australia. However, these studies have not provided conclusive evidence for an association between particular viral genotypes and the EV71-associated clinical entities. On the other hand, some studies indicate that host factors might be more important in EV71 pathogenesis. The objective of this study was to test whether that type I IFN might play a role in controlling EV71 infection.
In a murine EV71 infection model, we demonstrated that dexsamethosome treatment (5 mg/kg, i.p., day 2 or 3 after infection) exacerbated the clinical symptoms and increased tissue viral titer in EV71-infected mice (3-day-old, i.p. inoculated with 4 X 106 PFU). On the other hand, poly (I:C) (10 μg/mouse, i.p., 12 h before infection), a double-strand RNA analog which can induce type I interferon in vivo, protected mice against EV71 challenge. Poly (I:C) increased the survival rate and decreased tissue viral titers of EV71-infected mice. Poly (I:C) treatment also could increase both the percentage of B220+/CD11c+ cells and the expression of MHCⅡ molecule or IFN-α of dendritic cells. Furthermore, poly (I:C) but not EV71-infection increased type I IFN production in ICR mice. In other experiments, we used anti-murine-type I IFN antibody (10,000 IU/mouse, i.p. two times, 6 h before and 12h after infection) to neutralize endogenous type I IFN in EV71 infected-mice (1~2 × 106 PFU, i.p.). This treatment resulted in a lower survival rate and a higher tissue viral titer in virus-infected mice. In addition, administrated murine type I IFN recombinant protein to EV71-infected mice (10,000 IU/mouse, i.p. three times at post infection day 0, 1, 2; 1, 2, 3 or 3, 4, 5) demonstrated that type I IFN could protect mice from EV71 challenge while given only at early time point after infection.
In vitro, we found that type I interferon protected human cell lines including SK-N-SH (neuroblastoma), RD (rhabdomyosarcoma), and Caco-2 (colorectal adenocarcinoma) from virus cytopathic effect. Based on these studies, we believe that type I IFN should be one of the important host factor to influence disease progression of EV71 infection and that immediate IFN-α therapy may be considered as a treatment regimen.
Akaza, H. (1997). New strategy of bio-chemoprevention on recurrence of superficial bladder cancer based on a hypothesis of the mechanism of recurrence. Gan To Kagaku Ryoho 24 Suppl 1, 253-6.
Arnheiter, H., Frese, M., Kambadur, R., Meier, E. & Haller, O. (1996). Mx transgenic mice--animal models of health. Curr Top Microbiol Immunol 206, 119-47.
Arya, S. C. (2000). Antiviral therapy for neurological manifestations of enterovirus 71 infection. Clin Infect Dis 30, 988.
Bajcetic, M., Zigon, N., Samardzic, R. & Beleslin, D. B. (1998). [Alpha interferons--new therapeutic modalities]. Med Pregl 51, 135-9.
Barchet, W., Cella, M., Odermatt, B., Asselin-Paturel, C., Colonna, M. & Kalinke, U. (2002). Virus-induced interferon alpha production by a dendritic cell subset in the absence of feedback signaling in vivo. J Exp Med 195, 507-16.
Black, T. L., Barber, G. N. & Katze, M. G. (1993). Degradation of the interferon-induced 68,000-M(r) protein kinase by poliovirus requires RNA. J Virol 67, 791-800.
Blomberg, J., Lycke, E., Ahlfors, K., Johnsson, T., Wolontis, S. & von Zeipel, G. (1974). Letter: New enterovirus type associated with epidemic of aseptic meningitis and-or hand, foot, and mouth disease. Lancet 2, 112.
Cardosa, M. J., Krishnan, S., Tio, P. H., Perera, D. & Wong, S. C. (1999). Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak. Lancet 354, 987-91.
Chan, L. G., Parashar, U. D., Lye, M. S., Ong, F. G., Zaki, S. R., Alexander, J. P., Ho, K. K., Han, L. L., Pallansch, M. A., Suleiman, A. B., Jegathesan, M. & Anderson, L. J. (2000). Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group. Clin Infect Dis 31, 678-83.
Chang, H. W., Watson, J. C. & Jacobs, B. L. (1992). The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A 89, 4825-9.
Chang, L. Y., Hsia, S. H., Wu, C. T., Huang, Y. C., Lin, K. L., Fang, T. Y. & Lin, T. Y. (2004). Outcome of enterovirus 71 infections with or without stage-based management: 1998 to 2002. Pediatr Infect Dis J 23, 327-32.
Chang, L. Y., Lin, T. Y., Hsu, K. H., Huang, Y. C., Lin, K. L., Hsueh, C., Shih, S. R., Ning, H. C., Hwang, M. S., Wang, H. S. & Lee, C. Y. (1999). Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease. Lancet 354, 1682-6.
Chaudhuri, A. (2004). Adjunctive dexamethasone treatment in acute bacterial meningitis. Lancet Neurol 3, 54-62.
Colamonici, O. R., Domanski, P., Sweitzer, S. M., Larner, A. & Buller, R. M. (1995). Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon alpha transmembrane signaling. J Biol Chem 270, 15974-8.
Crotty, S., Hix, L., Sigal, L. J. & Andino, R. (2002). Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection. J Gen Virol 83, 1707-20.
Der, S. D., Zhou, A., Williams, B. R. & Silverman, R. H. (1998). Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci U S A 95, 15623-8.
Dragoje, S., Tolnay, M., Dalquen, P. & Probst, A. (1995). Brain irradiation and antioedematous dexamethasone treatment--risk factors for herpes simplex encephalitis? Schweiz Arch Neurol Psychiatr 146, 277-80.
Ferran, M. C. & Lucas-Lenard, J. M. (1997). The vesicular stomatitis virus matrix protein inhibits transcription from the human beta interferon promoter. J Virol 71, 371-7.
Gale, M., Jr., Tan, S. L. & Katze, M. G. (2000). Translational control of viral gene expression in eukaryotes. Microbiol Mol Biol Rev 64, 239-80.
Gallucci, S., Lolkema, M. & Matzinger, P. (1999). Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5, 1249-55.
Giron, D. J., Agostini, H. J. & Thomas, D. C. (1988). Effect of interferons and poly(I):poly(C) on the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in different mouse strains. J Interferon Res 8, 745-53.
Gobara, F., Itagaki, A., Ito, Y., Saito, K. & Katsumoto, T. (1977). Properties of virus isolated from an epidemic of hand-foot-and-mouth disease in 1973 in the city of Matsue. Comparison with Coxsackievirus group A type 16 prototype. Microbiol Immunol 21, 207-17.
Goodbourn, S., Didcock, L. & Randall, R. E. (2000). Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81, 2341-64.
Guggenheim, M. A. & Baron, S. (1977). Clinical studies of an interferon inducer, polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)], in children. J Infect Dis 136, 50-8.
Guha-Thakurta, N. & Majde, J. A. (1997). Early induction of proinflammatory cytokine and type I interferon mRNAs following Newcastle disease virus, poly [rI:rC], or low-dose LPS challenge of the mouse. J Interferon Cytokine Res 17, 197-204.
Hagiwara, A., Tagaya, I. & Yoneyama, T. (1978). Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Intervirology 9, 60-3.
Haig, D. M., McInnes, C. J., Thomson, J., Wood, A., Bunyan, K. & Mercer, A. (1998). The orf virus OV20.0L gene product is involved in interferon resistance and inhibits an interferon-inducible, double-stranded RNA-dependent kinase. Immunology 93, 335-40.
Haller, O., Acklin, M. & Staeheli, P. (1986). Genetic resistance to influenza virus in wild mice. Curr Top Microbiol Immunol 127, 331-7.
Hefti, H. P., Frese, M., Landis, H., Di Paolo, C., Aguzzi, A., Haller, O. & Pavlovic, J. (1999). Human MxA protein protects mice lacking a functional alpha/beta interferon system against La crosse virus and other lethal viral infections. J Virol 73, 6984-91.
Ho, M., Chen, E. R., Hsu, K. H., Twu, S. J., Chen, K. T., Tsai, S. F., Wang, J. R. & Shih, S. R. (1999). An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 341, 929-35.
Hoke, C. H., Jr., Vaughn, D. W., Nisalak, A., Intralawan, P., Poolsuppasit, S., Jongsawas, V., Titsyakorn, U. & Johnson, R. T. (1992). Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. J Infect Dis 165, 631-7.
Huang, C. C., Liu, C. C., Chang, Y. C., Chen, C. Y., Wang, S. T. & Yeh, T. F. (1999). Neurologic complications in children with enterovirus 71 infection. N Engl J Med 341, 936-42.
Huang, F. L., Jan, S. L., Chen, P. Y., Chi, C. S., Wang, T. M., Fu, Y. C., Tsai, C. R. & Chang, Y. (2002). Left ventricular dysfunction in children with fulminant enterovirus 71 infection: an evaluation of the clinical course. Clin Infect Dis 34, 1020-4.
Imani, F. & Jacobs, B. L. (1988). Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein. Proc Natl Acad Sci U S A 85, 7887-91.
Isaacs, A. & Lindenmann, J. (1957). Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147, 258-67.
Ishimaru, Y., Nakano, S., Yamaoka, K. & Takami, S. (1980). Outbreaks of hand, foot, and mouth disease by enterovirus 71. High incidence of complication disorders of central nervous system. Arch Dis Child 55, 583-8.
Ito, T., Amakawa, R., Inaba, M., Ikehara, S., Inaba, K. & Fukuhara, S. (2001). Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol 166, 2961-9.
Iwasaki, A., Welker, R., Mueller, S., Linehan, M., Nomoto, A. & Wimmer, E. (2002). Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infection. J Infect Dis 186, 585-92.
Jacobs, B. L. & Langland, J. O. (1996). When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology 219, 339-49.
Jouanguy, E., Altare, F., Lamhamedi-Cherradi, S. & Casanova, J. L. (1997). Infections in IFNGR-1-deficient children. J Interferon Cytokine Res 17, 583-7.
Katze, M. G., He, Y. & Gale, M., Jr. (2002). Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2, 675-87.
Kennett, M. L., Birch, C. J., Lewis, F. A., Yung, A. P., Locarnini, S. A. & Gust, I. D. (1974). Enterovirus type 71 infection in Melbourne. Bull World Health Organ 51, 609-15.
Kerr, I. M. & Brown, R. E. (1978). pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci U S A 75, 256-60.
Kirchner, H. (1984). Interferons, a group of multiple lymphokines. Springer Semin Immunopathol 7, 347-74.
Kirkwood, J. (2002). Cancer immunotherapy: the interferon-alpha experience. Semin Oncol 29, 18-26.
Komatsu, H., Shimizu, Y., Takeuchi, Y., Ishiko, H. & Takada, H. (1999). Outbreak of severe neurologic involvement associated with Enterovirus 71 infection. Pediatr Neurol 20, 17-23.
Komatsu, T., Takeuchi, K., Yokoo, J., Tanaka, Y. & Gotoh, B. (2000). Sendai virus blocks alpha interferon signaling to signal transducers and activators of transcription. J Virol 74, 2477-80.
Langland, J. O., Pettiford, S., Jiang, B. & Jacobs, B. L. (1994). Products of the porcine group C rotavirus NSP3 gene bind specifically to double-stranded RNA and inhibit activation of the interferon-induced protein kinase PKR. J Virol 68, 3821-9.
Le Bon, A. & Tough, D. F. (2002). Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 14, 432-6.
Limoges, J., Persidsky, Y., Bock, P. & Gendelman, H. E. (1997). Dexamethasone therapy worsens the neuropathology of human immunodeficiency virus type 1 encephalitis in SCID mice. J Infect Dis 175, 1368-81.
Lin, T. Y., Chang, L. Y., Hsia, S. H., Huang, Y. C., Chiu, C. H., Hsueh, C., Shih, S. R., Liu, C. C. & Wu, M. H. (2002a). The 1998 enterovirus 71 outbreak in Taiwan: pathogenesis and management. Clin Infect Dis 34 Suppl 2, S52-7.
Lin, T. Y., Chang, L. Y., Huang, Y. C., Hsu, K. H., Chiu, C. H. & Yang, K. D. (2002b). Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy. Acta Paediatr 91, 632-5.
Lin, T. Y., Hsia, S. H., Huang, Y. C., Wu, C. T. & Chang, L. Y. (2003). Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis 36, 269-74.
Lobigs, M., Mullbacher, A., Wang, Y., Pavy, M. & Lee, E. (2003). Role of type I and type II interferon responses in recovery from infection with an encephalitic flavivirus. J Gen Virol 84, 567-72.
Luft, T., Pang, K. C., Thomas, E., Hertzog, P., Hart, D. N., Trapani, J. & Cebon, J. (1998). Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol 161, 1947-53.
Lum, L. C., Chua, K. B., McMinn, P. C., Goh, A. Y., Muridan, R., Sarji, S. A., Hooi, P. S., Chua, B. H. & Lam, S. K. (2002). Echovirus 7 associated encephalomyelitis. J Clin Virol 23, 153-60.
Lum, L. C., Wong, K. T., Lam, S. K., Chua, K. B., Goh, A. Y., Lim, W. L., Ong, B. B., Paul, G., AbuBakar, S. & Lambert, M. (1998). Fatal enterovirus 71 encephalomyelitis. J Pediatr 133, 795-8.
McMinn, P., Lindsay, K., Perera, D., Chan, H. M., Chan, K. P. & Cardosa, M. J. (2001). Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in Malaysia, Singapore, and Western Australia. J Virol 75, 7732-8.
McMinn, P. C. (2002). An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26, 91-107.
Miller, D. M., Zhang, Y., Rahill, B. M., Waldman, W. J. & Sedmak, D. D. (1999). Human cytomegalovirus inhibits IFN-alpha-stimulated antiviral and immunoregulatory responses by blocking multiple levels of IFN-alpha signal transduction. J Immunol 162, 6107-13.
Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P. & Tough, D. F. (2002). Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263-71.
Mueller, S., Cao, X., Welker, R. & Wimmer, E. (2002). Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. J Biol Chem 277, 7897-904.
Nakaya, T., Sato, M., Hata, N., Asagiri, M., Suemori, H., Noguchi, S., Tanaka, N. & Taniguchi, T. (2001). Gene induction pathways mediated by distinct IRFs during viral infection. Biochem Biophys Res Commun 283, 1150-6.
Nolan, M. A., Craig, M. E., Lahra, M. M., Rawlinson, W. D., Prager, P. C., Williams, G. D., Bye, A. M. & Andrews, P. I. (2003). Survival after pulmonary edema due to enterovirus 71 encephalitis. Neurology 60, 1651-6.
Ooi, M. H., Wong, S. C., Clear, D., Perera, D., Krishnan, S., Preston, T., Tio, P. H., Willison, H. J., Tedman, B., Kneen, R., Cardosa, M. J. & Solomon, T. (2003). Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, Malaysia. Clin Infect Dis 36, 550-9.
Padalko, E., Nuyens, D., De Palma, A., Verbeken, E., Aerts, J. L., De Clercq, E., Carmeliet, P. & Neyts, J. (2004). The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis. Antimicrob Agents Chemother 48, 267-74.
Paquette, R. L., Hsu, N. C., Kiertscher, S. M., Park, A. N., Tran, L., Roth, M. D. & Glaspy, J. A. (1998). Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J Leukoc Biol 64, 358-67.
Pavlovic, J., Arzet, H. A., Hefti, H. P., Frese, M., Rost, D., Ernst, B., Kolb, E., Staeheli, P. & Haller, O. (1995). Enhanced virus resistance of transgenic mice expressing the human MxA protein. J Virol 69, 4506-10.
Pestka, S., Langer, J. A., Zoon, K. C. & Samuel, C. E. (1987). Interferons and their actions. Annu Rev Biochem 56, 727-77.
Poast, J., Seidel, H. M., Hendricks, M. D., Haslam, J. A., Levy, H. B. & Baron, S. (2002). Poly I:CLC induction of the interferon system in mice: an initial study of four detection methods. J Interferon Cytokine Res 22, 1035-40.
Pyo, S., Gangemi, J. D., Ghaffar, A. & Mayer, E. P. (1993). Poly I:C-induced antiviral and cytotoxic activities are mediated by different mechanisms. Int J Immunopharmacol 15, 477-86.
Renauld, J. C. (2003). Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators. Nat Rev Immunol 3, 667-76.
Rosztoczy, I. & Megyeri, K. (1989). Essentially pure murine interferon-alpha/beta primes poly rI:rC and Sendai virus-induced interferon production in mice. J Biol Regul Homeost Agents 3, 35-8.
Santini, S. M., Di Pucchio, T., Lapenta, C., Parlato, S., Logozzi, M. & Belardelli, F. (2002). The natural alliance between type I interferon and dendritic cells and its role in linking innate and adaptive immunity. J Interferon Cytokine Res 22, 1071-80.
Santini, S. M., Lapenta, C., Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T. & Belardelli, F. (2000). Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp Med 191, 1777-88.
Satomi, H., Wang, B., Fujisawa, H. & Otsuka, F. (2002). Interferon-beta from melanoma cells suppresses the proliferations of melanoma cells in an autocrine manner. Cytokine 18, 108-15.
Schmidt, K. N., Leung, B., Kwong, M., Zarember, K. A., Satyal, S., Navas, T. A., Wang, F. & Godowski, P. J. (2004). APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA. J Immunol 172, 138-43.
Shen, W. C., Tsai, C., Chiu, H. & Chow, K. (2000). MRI of Enterovirus 71 myelitis with monoplegia. Neuroradiology 42, 124-7.
Shih, S. R., Tsai, K. N., Li, Y. S., Chueh, C. C. & Chan, E. C. (2003). Inhibition of enterovirus 71-induced apoptosis by allophycocyanin isolated from a blue-green alga Spirulina platensis. J Med Virol 70, 119-25.
Sommer, J. B., Heckmann, J. G., Kraus, J., Neundorfer, B. & Erbguth, F. J. (2000). [Generalized brain edema in non-purulent meningoencephalitis. The anti-edema effect of therapy with dexamethasone]. Nervenarzt 71, 112-5.
Staeheli, P., Grob, R., Meier, E., Sutcliffe, J. G. & Haller, O. (1988). Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol Cell Biol 8, 4518-23.
Stojdl, D. F., Lichty, B., Knowles, S., Marius, R., Atkins, H., Sonenberg, N. & Bell, J. C. (2000). Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 6, 821-5.
Stojdl, D. F., Lichty, B. D., tenOever, B. R., Paterson, J. M., Power, A. T., Knowles, S., Marius, R., Reynard, J., Poliquin, L., Atkins, H., Brown, E. G., Durbin, R. K., Durbin, J. E., Hiscott, J. & Bell, J. C. (2003). VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell 4, 263-75.
Symons, J. A., Alcami, A. & Smith, G. L. (1995). Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 81, 551-60.
Thompson, S. R. & Sarnow, P. (2003). Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved. Virology 315, 259-66.
Wang, J. R., Tuan, Y. C., Tsai, H. P., Yan, J. J., Liu, C. C. & Su, I. J. (2002). Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. J Clin Microbiol 40, 10-5.
Wang, S. M., Lei, H. Y., Huang, K. J., Wu, J. M., Wang, J. R., Yu, C. K., Su, I. J. & Liu, C. C. (2003). Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 188, 564-70.
Wang, S. M., Liu, C. C., Tseng, H. W., Wang, J. R., Huang, C. C., Chen, Y. J., Yang, Y. J., Lin, S. J. & Yeh, T. F. (1999). Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin Infect Dis 29, 184-90.
Wang, X., Li, M., Zheng, H., Muster, T., Palese, P., Beg, A. A. & Garcia-Sastre, A. (2000). Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol 74, 11566-73.
Weber, F., Haller, O. & Kochs, G. (2000). MxA GTPase blocks reporter gene expression of reconstituted Thogoto virus ribonucleoprotein complexes. J Virol 74, 560-3.
Weihua, X., Ramanujam, S., Lindner, D. J., Kudaravalli, R. D., Freund, R. & Kalvakolanu, D. V. (1998). The polyoma virus T antigen interferes with interferon-inducible gene expression. Proc Natl Acad Sci U S A 95, 1085-90.
Wen, Y. Y., Chang, T. Y., Chen, S. T., Li, C. & Liu, H. S. (2003). Comparative study of enterovirus 71 infection of human cell lines. J Med Virol 70, 109-18.
Williams, B. R. (1999). PKR; a sentinel kinase for cellular stress. Oncogene 18, 6112-20.
Wu, J. M., Wang, J. N., Tsai, Y. C., Liu, C. C., Huang, C. C., Chen, Y. J. & Yeh, T. F. (2002). Cardiopulmonary manifestations of fulminant enterovirus 71 infection. Pediatrics 109, E26-.
Yan, J. J., Wang, J. R., Liu, C. C., Yang, H. B. & Su, I. J. (2000). An outbreak of enterovirus 71 infection in Taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis. J Clin Virol 17, 13-22.
Yang, K. D., Yang, M. Y., Li, C. C., Lin, S. F., Chong, M. C., Wang, C. L., Chen, R. F. & Lin, T. Y. (2001). Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis 183, 850-6.
Zhou, A., Paranjape, J. M., Der, S. D., Williams, B. R. & Silverman, R. H. (1999). Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Virology 258, 435-40.