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系統識別號 U0026-0402201322200400
論文名稱(中文) 研究醣類分子在腸病毒71型感染之角色
論文名稱(英文) Investigate the Role of Carbohydrates on Enterovirus 71 Infection
校院名稱 成功大學
系所名稱(中) 醫學檢驗生物技術學系碩博士班
系所名稱(英) Department of Medical Laboratory Science and Biotechnology
學年度 101
學期 1
出版年 102
研究生(中文) 姜志穎
研究生(英文) Zhi-Ying Jiang
電子信箱 tdmanutp@hotmail.com
學號 T36991024
學位類別 碩士
語文別 英文
論文頁數 80頁
口試委員 指導教授-張權發
口試委員-王貞仁
口試委員-楊文彬
中文關鍵字 腸病毒71型  氮基醣化  醣類衍生物 
英文關鍵字 enterovirus 71 (EV71)  glycosylation  sugar-derivatives 
學科別分類
中文摘要 腸病毒71型(EV71)屬於小RNA病毒科、腸病毒屬,且為一不具外套膜,帶有一條正股RNA之病毒。腸病毒71型臨床上會常引發五歲以下孩童的手足口症、泡疹性咽峽炎,有時甚至會伴隨嚴重的神經性併發症,甚至導致死亡。針對腸病毒71型,到目前為止還未研發出一有效的疫苗或治療方式。先前研究指出醣類分子在腸病毒71型感染中扮演重要的角色,此外,實驗室也曾經從病毒顆粒上鑑定出氮基醣類的結構,由軟體分析也可預測出外殼蛋白上可能發生氮基醣化的位點。但是整體而言,醣類在腸病毒71型中的分子功能及生理意義至今還未很明瞭。本研究著重於外殼蛋白氮基醣化對於病毒感染的重要性,以及探討醣類衍生物對於腸病毒71型感染細胞的抑制效果。首先我們針對結構蛋白(VP1-VP3)的氮基醣化位置基因進行點突變,觀察去除外殼蛋白氮基醣化是否造成腸病毒71型的對細胞感染的影響。我們針對腸病毒71型感染性克隆中的VP1-VP3,其兩個氮基醣化序列中鄰近天冬醯胺酸(Asn)的絲胺酸(Ser)/穌胺酸(Thr)進行一個或兩個的胺基酸取代,製造出重組的感染性克隆,接著進行轉移感染(transfection)生產帶有突變的腸病毒71型。我們發現重組過後的病毒其感染力及製造能力明顯下降,導致其無法順利地放大。此外,我們也將由中研院來的醣類衍生物進行MTT assay,確認其對於RD細胞存活率並無影響,再取出不具細胞毒性之化合物來進行病毒的結合試驗。藉由酵素免疫分析法與流式細胞儀測試分析我們發現KS-4 (L-man-BIN)、KS-10 (L-xyl-BIN)、KS-12(L-fuc-BIN)與PA-e等化合物均對於腸病毒71型結合至細胞有著隨濃度增加而抑制的效果,可惜的是抑制效果並不夠顯著。之後我們將會完成重組病毒對於細胞結合力與感染力的測試,用以探討氮基醣化對腸病毒真正的影響。
英文摘要 Enterovirus 71 (EV71) is a non-enveloped, positive single-stranded RNA virus belonging to the family Picornaviridae and genus Enterovirus. It is notable as one of the major causative agents for hand, foot and mouth disease (HFMD), herpangina and sometimes associated with severe neurological complications and deaths in children. So far there is no effective vaccine or treatment for EV71. Previous studies showed that carbohydrates played an important role on EV71 infection. The possible N-glycosylation sites on viral capsid proteins have also been predicted. But the molecular function and significance of glycans in EV71 were still unclear. The aims of this study were to explore the importance of N-glycosylation on the viral proteins and characterize the effect of the sugar-derivatives during the infection of EV71 to RD cells. We applied the site-mutagenesis on the genome of viral structural proteins to evaluate the effect of N-glycosylation on the EV71 infection. Single or double substitutions of serine/threonine next to the N-glycosylation asparagine on VP1, VP2 and VP3 genomes were constructed and transfected for virus production. Owing to the mutations, the recombinant viruses showed lower infectivity to RD cells and reduced propagation rate compared with wild-type. In addition, sugar-derivatives obtained from GRC, Academia Sinica were subjected for MTT assay. Compounds showed less cytotoxicity were then used for virus binding assay. Although the inhibition abilities of these compounds were not significant, some compounds, such as KS-4(L-man-BIN), KS-10(L-xyl-BIN), KS-12(L-fuc-BIN) and PA-e, showed good inhibitory effects with a dose-dependent manner by using ELISA assay and flow cytometry. The binding and infection features of the recombinant EV71 viruses will also be evaluated and confirmed in the furture.
論文目次 摘要…………………………………………………………………………..I
Abstract …………………………………………………………………...II
Acknowledgements ………………………………………………………III
Contents …………………………………………………………...............IV
List of Tables …………………………………………..……………..........VI
List of Figures ……………………………………….………………........VII
Chapter 1. Introduction ……….…………………….…………….……....1
The classification of EV71 ………..………............................…….…..1
The characteristics of EV71 …………….…………….……..…..…....2
The propagation of EV71 .………………………………......................3
The clinical manifestations and diagnosis of EV71 …………………...4
The prevention and treatment of EV71 ……...……………...…………5
The infectious clone system of virus ………………………….......…...6
The viruses and glycosylation ………………………………………....7
Chapter 2. Objectives and specific aims ………...…….………………...10
Chapter 3. Material and methods …...………………….…...…………..11
Cell and virus culture ……………………………………………..….11
Determination of virus titers ……………………………………..…..13
Component cell preparation ……………………………….......……..15
The construct of recombinant infectious clone ……………………....16
The generation of recombinant EV71 viruses ……………….......…...22
Western blotting …………………………………………..………….25
MTT assay to test the cytotoxicity of sugar-derivatives ….....……….27
Virus binding assay ……………………………..…………………....28
Chapter 4. Results ………………………………………………...……...30
The construct of mutant EV71 infectious clone ……………….…30
The production of recombinant de-glycosylated EV71 ……….…30
The screening for sugar-derivatives on the inhibitory effect of EV71 binding ………………….………………………………………...32
The potential compounds for the inhibition of EV71 binding to RD cells …………..…………………………………………………….32
Chapter 5. Discussions …………………………………………….……..34
Chapter 6. Conclusion …………………………...………….…….……...38
References …………………………………………………………............39
Tables ………………………………………………………........................48
Figures ……………………………………………………..........................53
Appendix ………………………………………………………..................66
參考文獻 1. Alen, M. M., T. De Burghgraeve, S. J. Kaptein, J. Balzarini, J. Neyts, and D. Schols. 2011. Broad antiviral activity of carbohydrate-binding agents against the four serotypes of dengue virus in monocyte-derived dendritic cells. PloS one 6:e21658.
2. Arita, M., N. Nagata, N. Iwata, Y. Ami, Y. Suzaki, K. Mizuta, T. Iwasaki, T. Sata, T. Wakita, and H. Shimizu. 2007. An attenuated strain of enterovirus 71 belonging to genotype a showed a broad spectrum of antigenicity with attenuated neurovirulence in cynomolgus monkeys. Journal of virology 81:9386-9395.
3. Bale, S., T. Liu, S. Li, Y. Wang, D. Abelson, M. Fusco, V. L. Woods, Jr., and E. O. Saphire. 2011. Ebola virus glycoprotein needs an additional trigger, beyond proteolytic priming for membrane fusion. PLoS neglected tropical diseases 5:e1395.
4. Bause, E. 1983. Structural requirements of N-glycosylation of proteins. Studies with proline peptides as conformational probes. The Biochemical journal 209:331-336.
5. Bible, J. M., P. Pantelidis, P. K. Chan, and C. Y. Tong. 2007. Genetic evolution of enterovirus 71: epidemiological and pathological implications. Reviews in medical virology 17:371-379.
6. Biering, S. B., A. Huang, A. T. Vu, L. R. Robinson, B. Bradel-Tretheway, E. Choi, B. Lee, and H. C. Aguilar. 2012. N-Glycans on the Nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization. Journal of virology 86:11991-12002.
7. Blomberg, J., E. Lycke, K. Ahlfors, T. Johnsson, S. Wolontis, and G. von Zeipel. 1974. Letter: New enterovirus type associated with epidemic of aseptic meningitis and-or hand, foot, and mouth disease. Lancet 2:112.
8. Boyer, J. C., and A. L. Haenni. 1994. Infectious transcripts and cDNA clones of RNA viruses. Virology 198:415-426.
9. Cermelli, C., A. Cuoghi, M. Scuri, C. Bettua, R. G. Neglia, A. Ardizzoni, E. Blasi, T. Iannitti, and B. Palmieri. 2011. In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid. Virology journal 8:141.
10. Chan, L. G., U. D. Parashar, M. S. Lye, F. G. Ong, S. R. Zaki, J. P. Alexander, K. K. Ho, L. L. Han, M. A. Pallansch, A. B. Suleiman, M. Jegathesan, and L. J. Anderson. 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 31:678-683.
11. Chen, C. H., B. M. Hsu, and M. T. Wan. 2008. Molecular detection and prevalence of enterovirus within environmental water in Taiwan. Journal of applied microbiology 104:817-823.
12. Chen, K. T., H. L. Chang, S. T. Wang, Y. T. Cheng, and J. Y. Yang. 2007. Epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in Taiwan, 1998-2005. Pediatrics 120:e244-252.
13. Chiu, C. H., C. Chu, C. C. He, and T. Y. Lin. 2006. Protection of neonatal mice from lethal enterovirus 71 infection by maternal immunization with attenuated Salmonella enterica serovar Typhimurium expressing VP1 of enterovirus 71. Microbes and infection / Institut Pasteur 8:1671-1678.
14. Chong, P., S. Y. Hsieh, C. C. Liu, A. H. Chou, J. Y. Chang, S. C. Wu, S. J. Liu, Y. H. Chow, I. J. Su, and M. Klein. 2012. Production of EV71 vaccine candidates. Human vaccines & immunotherapeutics 8.
15. Chung, Y. C., M. S. Ho, J. C. Wu, W. J. Chen, J. H. Huang, S. T. Chou, and Y. C. Hu. 2008. Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge. Vaccine 26:1855-1862.
16. De Jesus, N. H. 2007. Epidemics to eradication: the modern history of poliomyelitis. Virology journal 4:70.
17. Foo, D. G., S. Alonso, V. T. Chow, and C. L. Poh. 2007. Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing antibodies elicited by a synthetic peptide. Microbes and infection / Institut Pasteur 9:1299-1306.
18. Gilbert, G. L., K. E. Dickson, M. J. Waters, M. L. Kennett, S. A. Land, and M. Sneddon. 1988. Outbreak of enterovirus 71 infection in Victoria, Australia, with a high incidence of neurologic involvement. The Pediatric infectious disease journal 7:484-488.
19. Hall, R. N., J. Meers, E. Fowler, and T. Mahony. 2012. Back to BAC: the use of infectious clone technologies for viral mutagenesis. Viruses 4:211-235.
20. Hanna, S. L., T. C. Pierson, M. D. Sanchez, A. A. Ahmed, M. M. Murtadha, and R. W. Doms. 2005. N-linked glycosylation of west nile virus envelope proteins influences particle assembly and infectivity. Journal of virology 79:13262-13274.
21. Ho, M. 2000. Enterovirus 71: the virus, its infections and outbreaks. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 33:205-216.
22. 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. The New England journal of medicine 341:929-935.
23. Hsu, B. M., C. H. Chen, and M. T. Wan. 2008. Prevalence of enteroviruses in hot spring recreation areas of Taiwan. FEMS immunology and medical microbiology 52:253-259.
24. Huang, C. C. 2001. Neurologic complications of enterovirus 71 infection in children: lessons from this Taiwan epidemic. Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi 42:5-7.
25. Huang, S. W., D. Kiang, D. J. Smith, and J. R. Wang. 2011. Evolution of re-emergent virus and its impact on enterovirus 71 epidemics. Experimental biology and medicine 236:899-908.
26. Hussain, K. M., K. L. Leong, M. M. Ng, and J. J. Chu. 2011. The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71. The Journal of biological chemistry 286:309-321.
27. Johnson, A. J., F. Guirakhoo, and J. T. Roehrig. 1994. The envelope glycoproteins of dengue 1 and dengue 2 viruses grown in mosquito cells differ in their utilization of potential glycosylation sites. Virology 203:241-249.
28. Kaplan, G., A. Totsuka, P. Thompson, T. Akatsuka, Y. Moritsugu, and S. M. Feinstone. 1996. Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus. The EMBO journal 15:4282-4296.
29. Kato, D., S. Era, I. Watanabe, M. Arihara, N. Sugiura, K. Kimata, Y. Suzuki, K. Morita, K. I. Hidari, and T. Suzuki. 2010. Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antiviral research 88:236-243.
30. Kim, J. I., and M. S. Park. 2012. N-linked glycosylation in the hemagglutinin of influenza A viruses. Yonsei medical journal 53:886-893.
31. Kimura, T., M. Imamura, N. Hiraga, T. Hatakeyama, D. Miki, C. Noguchi, N. Mori, M. Tsuge, S. Takahashi, Y. Fujimoto, E. Iwao, H. Ochi, H. Abe, T. Maekawa, K. Arataki, C. Tateno, K. Yoshizato, T. Wakita, T. Okamoto, Y. Matsuura, and K. Chayama. 2008. Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice. The Journal of general virology 89:2108-2113.
32. Kung, Y. H., S. W. Huang, P. H. Kuo, D. Kiang, M. S. Ho, C. C. Liu, C. K. Yu, I. J. Su, and J. R. Wang. 2010. Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase. Virology 396:1-9.
33. Kuo, C. Y., K. S. Liao, Y. C. Liu, and W. B. Yang. 2011. Bis-indole derivatives for polysaccharide compositional analysis and chiral resolution of D-, L-monosaccharides by ligand exchange capillary electrophoresis using borate-cyclodextrin as a chiral selector. Molecules 16:1682-1694.
34. Kuo, R. L., S. H. Kung, Y. Y. Hsu, and W. T. Liu. 2002. Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death. The Journal of general virology 83:1367-1376.
35. Lambert, C., and R. Prange. 2007. Posttranslational N-glycosylation of the hepatitis B virus large envelope protein. Virology journal 4:45.
36. Lee, M. S., and L. Y. Chang. 2010. Development of enterovirus 71 vaccines. Expert review of vaccines 9:149-156.
37. Lei, X., X. Liu, Y. Ma, Z. Sun, Y. Yang, Q. Jin, B. He, and J. Wang. 2010. The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses. Journal of virology 84:8051-8061.
38. Li, S., J. Schulman, S. Itamura, and P. Palese. 1993. Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus. Journal of virology 67:6667-6673.
39. Lin, T. Y., S. J. Twu, M. S. Ho, L. Y. Chang, and C. Y. Lee. 2003. Enterovirus 71 outbreaks, Taiwan: occurrence and recognition. Emerging infectious diseases 9:291-293.
40. Lin, Y. W., S. W. Wang, Y. Y. Tung, and S. H. Chen. 2009. Enterovirus 71 infection of human dendritic cells. Experimental biology and medicine 234:1166-1173.
41. Liu, C. C., M. S. Guo, F. H. Lin, K. N. Hsiao, K. H. Chang, A. H. Chou, Y. C. Wang, Y. C. Chen, C. S. Yang, and P. C. Chong. 2011. Purification and characterization of enterovirus 71 viral particles produced from vero cells grown in a serum-free microcarrier bioreactor system. PloS one 6:e20005.
42. Liu, F., Q. Liu, Y. Cai, Q. Leng, and Z. Huang. 2011. Construction and characterization of an infectious clone of coxsackievirus A16. Virology journal 8:534.
43. McElroy, K. L., K. A. Tsetsarkin, D. L. Vanlandingham, and S. Higgs. 2005. Characterization of an infectious clone of the wild-type yellow fever virus Asibi strain that is able to infect and disseminate in mosquitoes. The Journal of general virology 86:1747-1751.
44. Mondotte, J. A., P. Y. Lozach, A. Amara, and A. V. Gamarnik. 2007. Essential role of dengue virus envelope protein N glycosylation at asparagine-67 during viral propagation. Journal of virology 81:7136-7148.
45. Nishimura, Y., M. Shimojima, Y. Tano, T. Miyamura, T. Wakita, and H. Shimizu. 2009. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nature medicine 15:794-797.
46. Ong, K. C., S. Devi, M. J. Cardosa, and K. T. Wong. 2010. Formaldehyde-inactivated whole-virus vaccine protects a murine model of enterovirus 71 encephalomyelitis against disease. Journal of virology 84:661-665.
47. Ooi, M. H., S. C. Wong, P. Lewthwaite, M. J. Cardosa, and T. Solomon. 2010. Clinical features, diagnosis, and management of enterovirus 71. Lancet neurology 9:1097-1105.
48. Patel, K. P., and J. M. Bergelson. 2009. Receptors identified for hand, foot and mouth virus. Nature medicine 15:728-729.
49. Pikora, C. A. 2004. Glycosylation of the ENV spike of primate immunodeficiency viruses and antibody neutralization. Current HIV research 2:243-254.
50. Plevka, P., R. Perera, J. Cardosa, R. J. Kuhn, and M. G. Rossmann. 2012. Crystal structure of human enterovirus 71. Science 336:1274.
51. Ranganathan, S., S. Singh, C. L. Poh, and V. T. Chow. 2002. The hand, foot and mouth disease virus capsid: sequence analysis and prediction of antigenic sites from homology modelling. Applied bioinformatics 1:43-52.
52. Reading, P. C., M. D. Tate, D. L. Pickett, and A. G. Brooks. 2007. Glycosylation as a target for recognition of influenza viruses by the innate immune system. Advances in experimental medicine and biology 598:279-292.
53. Ritchie, G., D. J. Harvey, F. Feldmann, U. Stroeher, H. Feldmann, L. Royle, R. A. Dwek, and P. M. Rudd. 2010. Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein. Virology 399:257-269.
54. Rossmann, M. G., E. Arnold, J. W. Erickson, E. A. Frankenberger, J. P. Griffith, H. J. Hecht, J. E. Johnson, G. Kamer, M. Luo, A. G. Mosser, and et al. 1985. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317:145-153.
55. Rossmann, M. G., Y. He, and R. J. Kuhn. 2002. Picornavirus-receptor interactions. Trends in microbiology 10:324-331.
56. Rossmann, M. G., and J. E. Johnson. 1989. Icosahedral RNA virus structure. Annual review of biochemistry 58:533-573.
57. Sawyer, M. H. 1999. Enterovirus infections: diagnosis and treatment. The Pediatric infectious disease journal 18:1033-1039; quiz 1040.
58. 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. The Journal of infectious diseases 129:304-309.
59. Semler, B. L., A. J. Dorner, and E. Wimmer. 1984. Production of infectious poliovirus from cloned cDNA is dramatically increased by SV40 transcription and replication signals. Nucleic acids research 12:5123-5141.
60. Shaw, E. D., A. Newton, A. W. Powell, and C. J. Friday. 1961. Fluorescent antigen-antibody reactions in Coxsackie and ECHO enteroviruses. Virology 15:208-210.
61. Shi, X., and R. M. Elliott. 2004. Analysis of N-linked glycosylation of hantaan virus glycoproteins and the role of oligosaccharide side chains in protein folding and intracellular trafficking. Journal of virology 78:5414-5422.
62. Sivasamugham, L. A., M. J. Cardosa, W. S. Tan, and K. Yusoff. 2006. Recombinant Newcastle Disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits. Journal of medical virology 78:1096-1104.
63. Solomon, T., P. Lewthwaite, D. Perera, M. J. Cardosa, P. McMinn, and M. H. Ooi. 2010. Virology, epidemiology, pathogenesis, and control of enterovirus 71. The Lancet infectious diseases 10:778-790.
64. Su, P. Y., Y. T. Liu, H. Y. Chang, S. W. Huang, Y. F. Wang, C. K. Yu, J. R. Wang, and C. F. Chang. 2012. Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells. BMC microbiology 12:162.
65. Sugrue, R. J. 2007. Viruses and glycosylation: an overview. Methods in molecular biology 379:1-13.
66. Sun, S., Q. Wang, F. Zhao, W. Chen, and Z. Li. 2011. Glycosylation site alteration in the evolution of influenza A (H1N1) viruses. PloS one 6:e22844.
67. Totani, M., K. Yoshii, H. Kariwa, and I. Takashima. 2011. Glycosylation of the envelope protein of West Nile Virus affects its replication in chicks. Avian diseases 55:561-568.
68. Tung, W. S., S. A. Bakar, Z. Sekawi, and R. Rosli. 2007. DNA vaccine constructs against enterovirus 71 elicit immune response in mice. Genetic vaccines and therapy 5:6.
69. Vigerust, D. J., and V. L. Shepherd. 2007. Virus glycosylation: role in virulence and immune interactions. Trends in microbiology 15:211-218.
70. Wang, J. R., Y. C. Tuan, H. P. Tsai, J. J. Yan, C. C. Liu, and I. J. Su. 2002. Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. Journal of clinical microbiology 40:10-15.
71. Wang, S. M., H. Y. Lei, M. C. Huang, L. Y. Su, H. C. Lin, C. K. Yu, J. L. Wang, and C. C. Liu. 2006. Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 37:47-52.
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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 29:184-190.
73. Wang, S. Y., T. L. Lin, H. Y. Chen, and T. S. Lin. 2004. Early and rapid detection of enterovirus 71 infection by an IgM-capture ELISA. Journal of virological methods 119:37-43.
74. Wang, X., W. Peng, J. Ren, Z. Hu, J. Xu, Z. Lou, X. Li, W. Yin, X. Shen, C. Porta, T. S. Walter, G. Evans, D. Axford, R. Owen, D. J. Rowlands, J. Wang, D. I. Stuart, E. E. Fry, and Z. Rao. 2012. A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. Nature structural & molecular biology 19:424-429.
75. Weng, T. Y., L. C. Chen, H. W. Shyu, S. H. Chen, J. R. Wang, C. K. Yu, H. Y. Lei, and T. M. Yeh. 2005. Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells. Antiviral research 67:31-37.
76. Yamayoshi, S., Y. Yamashita, J. Li, N. Hanagata, T. Minowa, T. Takemura, and S. Koike. 2009. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nature medicine 15:798-801.
77. Yang, B., H. Chuang, and K. D. Yang. 2009. Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells. Virology journal 6:141.
78. Yi, L., J. Lu, H. F. Kung, and M. L. He. 2011. The virology and developments toward control of human enterovirus 71. Critical reviews in microbiology 37:313-327.
79. 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. Journal of biomedical science 7:523-528.
80. Zeng, M., L. L. Jia, Y. X. Yu, G. M. Dong, W. X. Liu, Z. W. Wang, and D. F. Li. 2005. [Construction of infectious Japanese encephalitis virus clone based on the cDNA template of the attenuated live vaccine production strain SA14-14-2]. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 19:9-11.
81. Zhang, G., F. Zhou, B. Gu, C. Ding, D. Feng, F. Xie, J. Wang, C. Zhang, Q. Cao, Y. Deng, W. Hu, and K. Yao. 2012. In vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection. Archives of virology 157:669-679.
82. Zhang, M., B. Gaschen, W. Blay, B. Foley, N. Haigwood, C. Kuiken, and B. Korber. 2004. Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14:1229-1246.
83. Zhu, Q. C., Y. Wang, Y. P. Liu, R. Q. Zhang, X. Li, W. H. Su, F. Long, X. D. Luo, and T. Peng. 2011. Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 44:392-398.

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