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系統識別號 U0026-0812200910433226
論文名稱(中文) 嗜中性白血球在腸病毒71型感染中所扮演角色
論文名稱(英文) The role of neutrophils in enterovirus 71 infection
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 91
學期 2
出版年 92
研究生(中文) 郭書萍
研究生(英文) Sue-Ping Kuo
電子信箱 S4690404@ccmail.ncku.edu.tw
學號 S4690404
學位類別 碩士
語文別 英文
論文頁數 22頁
口試委員 口試委員-黎煥耀
口試委員-何美鄉
指導教授-陳舜華
中文關鍵字 嗜中性白血球  腸病毒七十一型  動物模式 
英文關鍵字 animal model  enterovirus71  neutrophils 
學科別分類
中文摘要 腸病毒七十一型主要感染對象為嬰兒及幼童,在臨床上病毒感染所造成的症狀有:手口足病、疱疹性咽峽炎、無菌性腦膜炎、腦炎、肢體麻痺,甚至死亡。但是目前對於腸病毒感染造成的疾病輕重程度與病人體內病毒數量的關係都還不太清楚。因此本研究首先藉著運用定量反轉錄-聚合酵素連鎖反應(QR-PCR)的建立來偵測腸病毒病人檢體中之病毒量。所利用的引子對腸病毒七十一型具有高度專一性,且所建立的腸病毒分析的敏感度可達每毫升檢體約可偵測103至106個正負股病毒基因組。我們收集並分析了20位病人的周邊單核血球細胞,但是卻偵測不到病毒的存在。除此外我們在老鼠上建立了餵食及腹腔注射感染的動物模式,發現不只是老鼠年齡影響了感染後存活率的多寡,而且老鼠的體重輕重也是存活率的因子之一。腸病毒在老鼠會造成全身性感染,病毒量又以神經性器官為最多。老鼠被感染的內臟,也有許多免疫細胞浸潤,例如嗜中性白血球,在一些病毒相關研究中指出,嗜中性白血球在一些好神經性病毒的感染中有著舉足輕重的角色,因此本實驗欲探討嗜中性白血球在腸病毒七十一型感染中所扮演的角色。所以接著當我們在餵食感染老鼠前後以嗜中性白血球專一抗體RB6-8C5來清除老鼠體內的嗜中性白血球後,發現老鼠的存活率降低了百分之五十五。在感染後7天後,在嗜中性白血球被清除且被病毒感染的老鼠中,腦及脊髓中病毒的量明顯的比只有被病毒感染的老鼠中來的高。研究結果顯示在餵食感染腸病毒七十一型的動物模式下,嗜中性白血球在避免老鼠感染後死亡及抑制病毒生長上有著相當重要的角色。

英文摘要 Enterovirus 71 (EV71) infection causes many clinical syndromes, including hand-foot-mouth disease, herpangina, aseptic meningitis, encephalitis, and paralysis, particularly, in infants and children. The relationship between disease progression and virus load is unclear. To investigate the virus load in serum samples collected from EV71 patients, I developed a reverse-transcription PCR assays to quantify EV71 genome in samples. These assays are specific for EV71. The detection limit is 103 copies genome per milliliter serum sample for both positive- and negative-stranded genome assays. When these assays were used to determine the amount of virus in peripheral blood mononuclear cells from 20 patients, no viruses can be detected in these samples. A mouse model was also established to investigate the pathogenesis of EV71 infection of intragastral (i.g.) or intraperitoneal (i.p.) inoculation. Results showed that the mouse survival rate was dependent on not only the age but also the body weight of mice. In EV71 infected-mice, viruses caused a systemic infection and their titers in neuronal organs were higher than those in non-neuronal organs during late infection. Immune cells, such as neutrophils, infiltrated into infected organs. Many reports indicated that neutrophils play an important in neurotropic virus infections. To investigate the role of neutrophils in EV71 infection, monoclonal antibody specific for granulocytes, RB6-8C5, was used to deplete neutrophils before and after oral infection with EV71. I found neutrophil depletion decreased mouse survival. The virus titer in the brain and spinal cord of neutrophil depleted mice was significantly higher than those of normal control mice at day 7 post infection. This result suggested that neutrophils play an important role in protecting mice from death and inhibiting virus growth after EV71 oral infection.

論文目次 Chinese abstract i
English abstract iii
Acknowledgement v
Contents vi
Introduction 1
Material and methods 6
Virus and cells 6
Preparation of total RNA from patient PBMC and virus-infected cells 6
Quantitative reverse-transcription polymerase chain reaction (QR-PCR) 7
Infection of mice and tissue collection 8
Antibody purification 8
Neutrophil depletion during EV71 infection 9
Immunohistochemistry (IHC) staining 10
Histological examination 10
Cocultivation of EV71 and neutrophils in vitro 10
Statistical analysis 11
Results 12
Determination of primers specificity 12
Establishment of RNA standards for QR-PCR 12
Analyses of PBMC from EV71 patients 13
Establishment of a mouse model for EV71 infection 13
The effect of neutrophil depletion on EV71-infected mice 16
Interaction of neutrophils and virus in vitro 17
Discussion 19
Detection of viruses in patient PBMC samples 19
Establishment of mouse model foe EV71 infection 20
The role of neutrophils in EV71 infection 21
References 23
Table 31
Figures 32
參考文獻 1. Abubakar, S., H. Y. Chee, N. Shafee, K. B. Chua, and S. K. Lam. 1999. Molecular detection of enteroviruses from an outbreak of hand, foot and mouth disease in Malaysia in 1997. Scand. J. Infect. Dis. 31:331-335.
2. Andino, R., G. E. Rieckhof, and D. Baltimore. 1990. A functional ribonucleoprotein complex forms around the 5' end of poliovirus RNA. Cell 63:369-380.
3. Basta, M., V. D. Miletic, C. H. Hammer, and M. M. Frank. 1996. Production and characterization of the monoclonal antibody against SGP120, a novel serum protein. Hybridoma 15:69-75.
4. Becq-Giraudon, B., A. Cremault, R. Marechaud, J. C. Abadie, M. Castets, and Y. Sudre. 1982. [Viral etiology of aseptic lymphocytic meningitis. Twenty-four cases seen over a nine-year period (author's transl)]. Sem. Hop. 58:739-745.
5. Blinzinger, K., J. Simon, and W. Muller. 1972. Discrepancies between the sites of replication and cytocidal action of encephalitogenic viruses. Experientia 28:97-98.
6. Brummer, E. 1989. The role of neutrophils and macrophages in host resistance to systemic fungal infections. Immunol. Ser. 47:273-89.:273-289.
7. Cassatella, M. A. 1995. The production of cytokines by polymorphonuclear neutrophils. Immunol. Today 16:21-26.
8. Chumakov, K. M., I. K. Lavrova, L. I. Martianova, M. B. Korolev, V. N. Bashkirtsev, and M. K. Voroshilova. 1979. Investigation of physicochemical properties of Bulgarian strain 258 of enterovirus type 71. Brief report. Arch. Virol. 60:359-362.
9. Chumakov, M., M. Voroshilova, L. Shindarov, I. Lavrova, L. Gracheva, G. Koroleva, S. Vasilenko, I. Brodvarova, M. Nikolova, S. Gyurova, M. Gacheva, G. Mitov, N. Ninov, E. Tsylka, I. Robinson, M. Frolova, V. Bashkirtsev, L. Martiyanova, and V. Rodin. 1979. Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch. Virol. 60:329-340.
10. Czuprynski, C. J., J. F. Brown, N. Maroushek, R. D. Wagner, and H. Steinberg. 1994. Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection. J. Immunol. 152:1836-1846.
23
11. Daher, K. A., M. E. Selsted, and R. I. Lehrer. 1986. Direct inactivation of viruses by human granulocyte defensins. J. Virol. 60:1068-1074.
12. Douglas, R. G., Jr., R. H. Alford, T. R. Cate, and R. B. Couch. 1966. The leukocyte response during viral respiratory illness in man. Ann. Intern. Med. 64:521-530.
13. Faden, H., J. J. Hong, and P. L. Ogra. 1984. Interaction of polymorphonuclear leukocytes and viruses in humans: adherence of polymorphonuclear leukocytes to respiratory syncytial virus-infected cells. J. Virol. 52:16-23.
14. Fleming, T. J., M. L. Fleming, and T. R. Malek. 1993. Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. J. Immunol. 151:2399-2408.
15. Fujii, T. and Y. Hirabayashi. 1999. Histochemical studies of glycosaminoglycans in developing periodontal ligaments of ICR mice. Anat. Rec. 254:465-473.
16. Ganz, T., M. E. Selsted, D. Szklarek, S. S. Harwig, K. Daher, D. F. Bainton, and R. I. Lehrer. 1985. Defensins. Natural peptide antibiotics of human neutrophils. J. Clin. Invest 76:1427-1435.
17. Green, I., C. H. Kirkpatrick, and D. C. Dale. 1971. Lactoferrin--specific localization in the nuclei of human polymorphonuclear neutrophilic leukocytes. Proc. Soc. Exp. Biol. Med. 137:1311-1317.
18. Hagiwara, A., I. Tagaya, and T. Yoneyama. 1978. Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Intervirology 9:60-63.
19. Hara, K., M. Ikeda, S. Saito, S. Matsumoto, K. Numata, N. Kato, K. Tanaka, and H. Sekihara. 2002. Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes. Hepatol. Res. 24:228.
20. Harmsen, M. C., P. J. Swart, M. P. de Bethune, R. Pauwels, E. De Clercq, T. H. The, and D. K. Meijer. 1995. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J. Infect. Dis. 172:380-388.
21. Hart, P. H., L. K. Spencer, M. F. Nulsen, P. J. McDonald, and J. J. Finlay-Jones. 1986. Neutrophil activity in abscess-bearing mice: comparative studies with neutrophils isolated from peripheral blood, elicited peritoneal exudates, and abscesses. Infect. Immun. 51:936-941.
24
22. Hestdal, K., F. W. Ruscetti, J. N. Ihle, S. E. Jacobsen, C. M. Dubois, W. C. Kopp, D. L. Longo, and J. R. Keller. 1991. Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. J. Immunol. 147:22-28.
23. Ho, M. 2000. Enterovirus 71: the virus, its infections and outbreaks. J. Microbiol. Immunol. Infect. 33:205-216.
24. Ho, M., E. R. Chen, K. H. Hsu, S. J. Twu, K. T. Chen, S. F. Tsai, J. R. Wang, and S. R. Shih. 1999. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N. Engl. J. Med. 341:929-935.
25. Holland, J. J., D. Kohne, and M. V. Doyle. 1973. Analysis of virus replication in ageing human fibroblast cultures. Nature 245:316-319.
26. Hsiung, G. D. and J. R. Wang. 2000. Enterovirus infections with special reference to enterovirus 71. J. Microbiol. Immunol. Infect. 33:1-8.
27. Hsueh, C., S. M. Jung, S. R. Shih, T. T. Kuo, W. J. Shieh, S. Zaki, T. Y. Lin, L. Y. Chang, H. C. Ning, and D. C. Yen. 2000. Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies. Mod. Pathol. 13:1200-1205.
28. Hyypia, T., T. Hovi, N. J. Knowles, and G. Stanway. 1997. Classification of enteroviruses based on molecular and biological properties. J. Gen. Virol. 78:1-11.
29. Ihara, T., M. Ito, and S. E. Starr. 1986. Human lymphocyte, monocyte and polymorphonuclear leucocyte mediated antibody-dependent cellular cytotoxicity against varicella-zoster virus-infected targets. Clin. Exp. Immunol. 63:179-187.
30. Jarzabek, Z. J., W. Sadowski, and P. Janicki. 1977. Characteristics of poliovirus type 3 strains after passage through monkey central nervous system. Acta Virol. 21 :57-62.
31. Kantarci, A. and T. E. Van Dyke. 2002. Neutrophil-mediated host response to Porphyromonas gingivalis. J. Int. Acad. Periodontol. 4:119-125.
32. Kennett, M. L., C. J. Birch, F. A. Lewis, A. P. Yung, S. A. Locarnini, and I. D. Gust. 1974. Enterovirus type 71 infection in Melbourne. Bull. World Health Organ 51 :609-615.
25
33. Kramer, M. F. and D. M. Coen. 1995. Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus. J. Virol. 69:1389-1399.
34. Lambertsen, K. L., R. Gregersen, N. Drojdahl, T. Owens, and B. Finsen. 2001. A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system. Brain Res. Brain Res. Protoc. 7:175-191.
35. Landry, M. L., S. N. Fonseca, S. Cohen, and C. W. Bogue. 1995. Fatal enterovirus type 71 infection: rapid detection and diagnostic pitfalls. Pediatr. Infect. Dis. J. 14:1095-1100.
36. Lehrer, R. I. and T. Ganz. 2002. Defensins of vertebrate animals. Curr. Opin. Immunol. 14:96-102.
37. Li, C. C., M. Y. Yang, R. F. Chen, T. Y. Lin, K. C. Tsao, H. C. Ning, H. C. Liu, S. F. Lin, W. T. Yeh, Y. T. Chu, and K. D. Yang. 2002. Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan. Scand. J. Infect. Dis. 34:104-109.
38. Lin, T. Y., C. Chu, and C. H. Chiu. 2002. Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro. J. Infect. Dis. 186:1161-1164.
39. Lin, T. Y., C. Chu, and C. H. Chiu. 2002. Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro. J. Infect. Dis. 186:1161-1164.
40. Lin, T. Y., S. H. Hsia, Y. C. Huang, C. T. Wu, and L. Y. Chang. 2003. Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin. Infect. Dis. 36:269-274.
41. Lin, Y. C., C. N. Wu, S. R. Shih, and M. S. Ho. 2002. Characterization of a Vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine 20:2485-2493.
42. Liu, C. C., H. W. Tseng, S. M. Wang, J. R. Wang, and I. J. Su. 2000. An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations. J. Clin. Virol. 17:23-30.
43. Lu, C. Y., C. Y. Lee, C. L. Kao, W. Y. Shao, P. I. Lee, S. J. Twu, C. C. Yeh, S. C. Lin, W. Y. Shih, S. I. Wu, and L. M. Huang. 2002. Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan. J. Med. Virol. 67 :217-223.
26
44. Lum, L. C., K. T. Wong, S. K. Lam, K. B. Chua, and A. Y. Goh. 1998. Neurogenic pulmonary oedema and enterovirus 71 encephalomyelitis. Lancet 352:1391.
45. MacGregor, R. R., H. M. Friedman, E. J. Macarak, and N. A. Kefalides. 1980. Virus infection of endothelial cells increases granulocyte adherence. J. Clin. Invest 65 :1469-1477.
46. Marchetti, M., C. Longhi, M. P. Conte, S. Pisani, P. Valenti, and L. Seganti. 1996. Lactoferrin inhibits herpes simplex virus type 1 adsorption to Vero cells. Antiviral Res. 29:221-231.
47. Mazza, G., W. P. Duffus, C. J. Elson, C. R. Stokes, A. D. Wilson, and A. H. Whiting. 1993. The separation and identification by monoclonal antibodies of dog IgG fractions. J. Immunol. Methods 161:193-203.
48. Melnick, J. L. and C. A. Phillips. 1970. Enteroviruses: vaccines, epidemiology, diagnosis, classification. CRC Crit Rev. Clin. Lab Sci. 1:87-118.
49. Minor, P. D., G. C. Schild, J. Bootman, D. M. Evans, M. Ferguson, P. Reeve, M. Spitz, G. Stanway, A. J. Cann, R. Hauptmann, L. D. Clarke, R. C. Mountford, and J. W. Almond. 1983. Location and primary structure of a major antigenic site for poliovirus neutralization. Nature 301:674-679.
50. Morrison, L. A., R. L. Sidman, and B. N. Fields. 1991. Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers. Proc. Natl. Acad. Sci. U. S. A 88:3852-3856.
51. Nagata, N., H. Shimizu, Y. Ami, Y. Tano, A. Harashima, Y. Suzaki, Y. Sato, T. Miyamura, T. Sata, and T. Iwasaki. 2002. Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71. J. Med. Virol. 67:207-216.
52. Nagy, G., S. Takatsy, E. Kukan, I. Mihaly, and I. Domok. 1982. Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Arch. Virol. 71:217-227.
53. Oberste, M. S., K. Maher, D. R. Kilpatrick, and M. A. Pallansch. 1999. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J. Virol. 73:1941-1948.
27
54. Okada, S., K. Tanaka, T. Sato, H. Ueno, S. Saito, T. Okusaka, K. Sato, S. Yamamoto, and T. Kakizoe. 2002. Dose-response Trial of Lactoferrin in Patients with Chronic Hepatitis C. Jpn. J. Cancer Res. 93:1063-1069.
55. Pastor, J., R. Cuenca, R. Velarde, I. Marco, L. Vinas, and S. Lavin. 1998. Evaluation of a haematological analyser (Sysmex F-800) with equine blood. Zentralbl. Veterinarmed. A 45:119-126.
56. Pelletier, J. and N. Sonenberg . 1988. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334:320-325.
57. Percy, N., G. J. Belsham, J. K. Brangwyn, M. Sullivan, D. M. Stone, and J. W. Almond. 1992. Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis. J. Virol. 66:1695-1701.
58. Ratcliffe, D. R., S. L. Nolin, and E. B. Cramer. 1988. Neutrophil interaction with influenza-infected epithelial cells. Blood 72:142-149.
59. Rogers, H. W. and E. R. Unanue . 1993. Neutrophils are involved in acute, nonspecific resistance to Listeria monocytogenes in mice. Infect. Immun. 61:5090-5096.
60. Rouse, B. T., L. A. Babiuk, and P. M. Henson. 1980. Neutrophils in antiviral immunity: inhibition of virus replication by a mediator produced by bovine neutrophils. J. Infect. Dis. 141:223-232.
61. Saxena, S. K., A. Singh, and A. Mathur. 2000. Antiviral effect of nitric oxide during Japanese encephalitis virus infection. Int. J. Exp. Pathol. 81:165-172.
62. Schmidt, N. J., E. H. Lennette, and H. H. Ho. 1974. An apparently new enterovirus isolated from patients with disease of the central nervous system. J. Infect. Dis. 129:304-309.
63. Shih, S. R., Y. S. Li, C. C. Chiou, P. C. Suen, T. Y. Lin, L. Y. Chang, Y. C. Huang, K. C. Tsao, H. C. Ning, T. Z. Wu, and E. C. Chan. 2000. Expression of capsid [correction of caspid] protein VP1 for use as antigen for the diagnosis of enterovirus 71 infection. J. Med. Virol. 61:228-234.
64. Sicinski, P., J. Rowinski, J. B. Warchol, Z. Jarzabek, W. Gut, B. Szczygiel, K. Bielecki, and G. Koch. 1990. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology 98:56-58.
28
65. Smith, J. A. 1994. Neutrophils, host defense, and inflammation: a double-edged sword. J. Leukoc. Biol. 56:672-686.
66. Srivastava, S., N. Khanna, S. K. Saxena, A. Singh, A. Mathur, and T. N. Dhole. 1999. Degradation of Japanese encephalitis virus by neutrophils. Int. J. Exp. Pathol. 80:17-24.
67. Tagaya, I. and K. Tachibana. 1975. Epidemic of hand, foot and mouth disease in Japan, 1972-1973: difference in epidemiologic and virologic features from the previous one. Jpn. J. Med. Sci. Biol. 28:231-234.
68. Tumpey, T. M., S. H. Chen, J. E. Oakes, and R. N. Lausch. 1996. Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea. J. Virol. 70:898-904.
69. Tumpey, T. M., S. H. Chen, J. E. Oakes, and R. N. Lausch. 1996. Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea. J. Virol. 70:898-904.
70. van Strijp, J. A., K. P. van Kessel, L. A. Miltenburg, A. C. Fluit, and J. Verhoef. 1988. Attachment of human polymorphonuclear leukocytes to herpes simplex virus-infected fibroblasts mediated by antibody-independent complement activation. J. Virol. 62:847-850.
71. Wang, J. R., H. P. Tsai, P. F. Chen, Y. J. Lai, J. J. Yan, D. Kiang, K. H. Lin, C. C. Liu, and I. J. Su. 2000. An outbreak of enterovirus 71 infection in Taiwan, 1998. II. Laboratory diagnosis and genetic analysis. J. Clin. Virol. 17:91-99.
72. Wang, S. M., C. C. Liu, H. W. Tseng, J. R. Wang, C. C. Huang, Y. J. Chen, Y. J. Yang, S. J. Lin, and T. F. Yeh . 1999. Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin. Infect. Dis. 29:184-190.
73. Wen, Y. Y., T. Y. Chang, S. T. Chen, C. Li, and H. S. Liu. 2003. Comparative study of enterovirus 71 infection of human cell lines. J. Med. Virol. 70:109-118.
74. Wolf, J. L., D. H. Rubin, R. Finberg, R. S. Kauffman, A. H. Sharpe, J. S. Trier, and B. N. Fields. 1981. Intestinal M cells: a pathway for entry of reovirus into the host. Science 212:471-472.
29
75. Wu, C. N., Y. C. Lin, C. Fann, N. S. Liao, S. R. Shih, and M. S. Ho. 2001. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus. Vaccine 20:895-904.
76. Wu, T. N., S. F. Tsai, S. F. Li, T. F. Lee, T. M. Huang, M. L. Wang, K. H. Hsu, and C. Y. Shen. 1999. Sentinel surveillance for enterovirus 71, Taiwan, 1998. Emerg. Infect. Dis. 5:458-460.
77. Wyatt, H. V. 1990. Incubation of poliomyelitis as calculated from the time of entry into the central nervous system via the peripheral nerve pathways. Rev. Infect. Dis. 12:547-556.
78. Yan, J. J., I. J. Su, P. F. Chen, C. C. Liu, C. K. Yu, and J. R. Wang. 2001. Complete genome analysis of enterovirus 71 isolated from an outbreak in Taiwan and rapid identification of enterovirus 71 and coxsackievirus A16 by RT-PCR. J. Med. Virol. 65:331-339.
79. Yan, J. J., I. J. Su, P. F. Chen, C. C. Liu, C. K. Yu, and J. R. Wang. 2001. Complete genome analysis of enterovirus 71 isolated from an outbreak in Taiwan and rapid identification of enterovirus 71 and coxsackievirus A16 by RT-PCR. J. Med. Virol. 65:331-339. 80. Yan, J. J., J. R. Wang, C. C. Liu, H. B. Yang, and I. J. Su. 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.
81. Yu, C. K., C. C. Chen, C. L. Chen, J. R. Wang, C. C. Liu, J. J. Yan, and I. J. Su. 2000. Neutralizing antibody provided protection against enterovirus type 71 lethal challenge in neonatal mice. J. Biomed. Sci. 7:523-528.
82. Zhang, L., W. Yu, T. He, J. Yu, R. E. Caffrey, E. A. Dalmasso, S. Fu, T. Pham, J. Mei, J. J. Ho, W. Zhang, P. Lopez, and D. D. Ho. 2002. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298:995-1000.
83. Zoll, G. J., W. J. Melchers, H. Kopecka, G. Jambroes, H. J. van der Poel, and J. M. Galama. 1992. General primer-mediated polymerase chain reaction for detection of enteroviruses: application for diagnostic routine and persistent infections. J. Clin. Microbiol. 30:160-165.
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