腸病毒71型(Enterovirus 71)是手足口症最常見的病原之一，是目前已知六十幾種的腸病毒中致病力最高且最易引發神經性併發症的一種，對於五歲以下的幼童更具有高致死率。在台灣每隔數年便有疫情傳出，2012年也曾爆發大規模流行，重症案例高達一百五十九例，因此腸病毒71型的疫苗開發更顯迫切。我們過去開發以重組桿狀病毒/昆蟲細胞表現系統來生產腸病毒71型類病毒顆粒疫苗，此類病毒顆粒雖然在大小、外觀與蛋白組成上與真實病毒外殼相似，但由於缺乏包裹病毒RNA的來源與機制，因此外殼VP0蛋白沒有包裹RNA所引起的自發性切割為VP2及VP4蛋白，無法形成成熟的病毒外殼。未成熟的腸病毒顆粒在免疫抗原性及顆粒穩定性上皆可能較成熟顆粒為差，因此本研究中我們嘗試建構一系列的重組桿狀病毒，以表現腸病毒71型病毒顆粒包裹RNA的必要蛋白與合成RNA，形成有包裹RNA的合成腸病毒71型類病毒顆粒，來引發VP0蛋白正確切割提升類病毒顆粒的免疫抗原性及顆粒穩定性，增加腸病毒71型類病毒顆粒疫苗的競爭力，但結果顯示我們的實驗設計無法生產有包裹RNA並且引發VP0蛋白切割的合成腸病毒71型類病毒顆粒。

摘要 I
Abstract II
目錄 III
圖表目錄 VII
第一章 文獻回顧 1
1-1 腸病毒71型(Enterovirus 71) 1
1-1-1 腸病毒71型的分類 1
1-1-2 腸病毒71型的流行病學 1
1-1-3 腸病毒71型的結構 2
1-1-4 腸病毒71型的病毒RNA包裹機制 3
1-2 腸病毒71型的疫苗發展(Enterovirus 71) 4
1-2-1 腸病毒71型類病毒顆粒疫苗 5
1-2-2 腸病毒71型類病毒顆粒疫苗的缺陷 6
1-3 重組桿狀病毒/昆蟲細胞表現系統 7
1-3-1 桿狀病毒 7
1-3-2 FLASHBACGOLD™重組桿狀病毒表現系統 8
1-4 研究動機 9
第二章 材料與方法 19
2-1 重組桿狀病毒的建構 19
2-1-1 FLASHBACGOLD™轉殖載體的建構 19
2-1-2 新型FLASHBACGOLD™轉殖載體的建構 22
2-1-3 桿狀病毒基因體重組 24
2-1-4 重組桿狀病毒的放大 25
2-1-5 終點稀釋法定量重組桿狀病毒效價 25
2-2 昆蟲細胞培養 25
2-3 重組桿狀病毒基因表現的分析 26
2-3-1 反轉錄聚合酶鏈式反應(REVERSE TRANSCRIPTION-PCR, RT-PCR) 26
2-4 合成腸病毒71型類病毒顆粒的生產 27
2-5 合成腸病毒71型類病毒顆粒的純化 27
2-5-1 切向流過濾系統(TANGENTIAL FLOW FILTRATION, TFF) 27
2-5-2 氯化銫不連續濃度梯度超高速離心法 28
2-5-3 蔗糖連續濃度梯度超高速離心法 29
2-6 合成腸病毒71型類病毒顆粒的外殼蛋白質分析 30
2-6-1 SDS-PAGE電泳分離 30
2-6-2 西方點墨法 31
2-7 合成腸病毒71型類病毒顆粒的分析 32
2-7-1 反轉錄聚合酶鏈式反應(REVERSE TRANSCRIPTION-PCR, RT-PCR) 32
第三章 實驗結果 49
3-1 重組桿狀病毒建構 49
3-1-1 建構BACF-EP23重組桿狀病毒 49
3-1-2 建構BACF-3B及BACF-2C重組桿狀病毒 50
3-1-3 BACF-EP23重組桿狀病毒在昆蟲細胞內的RNA轉錄情形 50
3-2 篩選合成腸病毒71型類病毒顆粒的生產條件 51
3-3 純化合成腸病毒71型類病毒顆粒 53
3-4 分析合成腸病毒71型類病毒顆粒的外殼蛋白組成 54
3-5 分析合成腸病毒71型類病毒顆粒內的RNA 54
3-6 第一階段實驗結果討論 55
3-6-1 昆蟲細胞的5’-CAPPING系統影響VPG-RNA複合物的形成 55
3-6-2 不連續的氯化銫濃度梯度影響超高速離心純化的效果 56
3-6-3 BACF-EP23重組桿狀病毒在昆蟲細胞內的RNA轉錄情形 57
3-6-4 高桿狀病毒劑量造成純化合成腸病毒71型病毒顆粒的困難 57
3-7 新型重組桿狀病毒的建構 58
3-7-1 PBACF-T7-EP23質體在細胞體外(IN VITRO)的RNA轉錄情形 59
3-7-2 BACF-T7-EP23重組桿狀病毒在昆蟲細胞內的RNA轉錄情形 60
3-8 生產及純化新型合成腸病毒71型類病毒顆粒 60
3-9 萃取新型合成腸病毒71型類病毒顆粒內的RNA 62
3-10 調整新型合成腸病毒71型類病毒顆粒的生產條件 62
第四章 結果討論 81
4-1 2CATPase蛋白無法組成複製複合體 (Repilication complex) 81
4-2 與本研究相似的文獻比較 82
4-3 同時共感染四支桿狀病毒至同一細胞有困難度 83
4-4 結論 83
第五章 參考文獻 85

Ansardi DC, Morrow CD. 1995. Amino acid substitutions in the poliovirus maturation cleavage site affect assembly and result in accumulation of provirions. J Virol 69(3):1540-1547.
Ansardi DC, Porter DC, Anderson MJ, Morrow CD. 1996. Poliovirus assembly and encapsidation of genomic RNA. Adv Virus Res 46:1-68.
Ansardi DC, Porter DC, Morrow CD. 1991. Coinfection with recombinant vaccinia viruses expressing poliovirus P1 and P3 proteins results in polyprotein processing and formation of empty capsid structures. J Virol 65(4):2088-2092.
Arnold E, Luo M, Vriend G, Rossmann MG, Palmenberg AC, Parks GD, Nicklin MJ, Wimmer E. 1987. Implications of the picornavirus capsid structure for polyprotein processing. Proc Natl Acad Sci U S A 84(1):21-25.
Basavappa R, Syed R, Flore O, Icenogle JP, Filman DJ, Hogle JM. 1994. Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: structure of the empty capsid assembly intermediate at 2.9 A resolution. Protein Sci 3(10):1651-1669.
Bedard KM, Semler BL. 2004. Regulation of picornavirus gene expression. Microbes Infect 6(7):702-713.
Borodavka A, Tuma R, Stockley PG. 2013. A two-stage mechanism of viral RNA compaction revealed by single molecule fluorescence. RNA Biol 10(4):481-489.
Brown BA, Oberste MS, Alexander JP, Jr., Kennett ML, Pallansch MA. 1999. Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J Virol 73(12):9969-9975.
Brown BA, Pallansch MA. 1995. Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Res 39(2-3):195-205.
Buenz EJ, Howe CL. 2006. Picornaviruses and cell death. Trends Microbiol 14(1):28-36.
Buonaguro L, Visciano ML, Tornesello ML, Tagliamonte M, Biryahwaho B, Buonaguro FM. 2005. Induction of systemic and mucosal cross-clade neutralizing antibodies in BALB/c mice immunized with human immunodeficiency virus type 1 clade A virus-like particles administered by different routes of inoculation. J Virol 79(11):7059-7067.
Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, Cho H, McMinn P. 2003. Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes. Emerg Infect Dis 9(4):461-468.
Caro V, Guillot S, Delpeyroux F, Crainic R. 2001. Molecular strategy for 'serotyping' of human enteroviruses. J Gen Virol 82(Pt 1):79-91.
Casal JI. 1999. Use of parvovirus-like particles for vaccination and induction of multiple immune responses. Biotechnol. Appl. Biochem. 29:141-150.
Chang LY, Lin TY, Hsu KH, Huang YC, Lin KL, Hsueh C, Shih SR, Ning HC, Hwang MS, Wang HS and others. 1999. Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease. Lancet 354(9191):1682-1686.
Chen CS, Yao YC, Lin SC, Lee YP, Wang YF, Wang JR, Liu CC, Lei HY, Yu CK. 2007. Retrograde axonal transport: a major transmission route of enterovirus 71 in mice. J Virol 81(17):8996-9003.
Chong P, Hsieh SY, Liu CC, Chou AH, Chang JY, Wu SC, Liu SJ, Chow YH, Su IJ, Klein M. 2012. Production of EV71 vaccine candidates. Hum Vaccin Immunother 8(12):1775-1783.
Chung YC, Ho MS, Wu JC, Chen WJ, Huang JH, Chou ST, Hu YC. 2008. Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge. Vaccine 26(15):1855-1862.
Chung YC, Huang JH, Lai CW, Sheng HC, Shih SR, Ho MS, Hu YC. 2006. Expression, purification and characterization of enterovirus-71 virus-like particles. World J Gastroenterol 12(6):921-927.
Cole CN, Smoler D, Wimmer E, Baltimore D. 1971. Defective interfering particles of poliovirus. I. Isolation and physical properties. J Virol 7(4):478-485.
Curry S, Fry E, Blakemore W, Abu-Ghazaleh R, Jackson T, King A, Lea S, Newman J, Stuart D. 1997. Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus. J Virol 71(12):9743-9752.
De Jesus NH. 2007. Epidemics to eradication: the modern history of poliomyelitis. Virol J 4:70.
Deshpande JM, Nadkarni SS, Francis PP. 2003. Enterovirus 71 isolated from a case of acute flaccid paralysis in India represents a new genotype. Current Science 84(10):1350-1353.
Dorner AJ, Dorner LF, Larsen GR, Wimmer E, Anderson CW. 1982. Identification of the initiation site of poliovirus polyprotein synthesis. J Virol 42(3):1017-28.
Fernandez-Tomas CB, Baltimore D. 1973. Morphogenesis of poliovirus. II. Demonstration of a new intermediate, the proviron. J Virol 12(5):1122-1130.
Fernandez-Tomas CB, Guttman N, Baltimore D. 1973. Morphogenesis of poliovirus 3. Formation of provirion in cell-free extracts. J Virol 12(5):1181-1183.
Gilbert SC. 2001. Virus-like particles as vaccine adjuvants. Mol Biotechnol 19(2):169-177.
Harmann CM, Schwimmbeck PL, Mertens T, Schulthesiss HP, Strauer BE. 1994. Identification of serotype-specific and nonserotype-specific B-Cell epitopes of coxsackie B virus using synthetic peptides. Virology. 200:381-389.
Hitchman RB, Possee RD, Siaterli E, Richards KS, Clayton AJ, Bird LE, Owens RJ, Carpentier DC, King FL, Danquah JO and others. 2010. Improved expression of secreted and membrane-targeted proteins in insect cells. Biotechnol Appl Biochem 56(3):85-93.
Hodgson JJ, Arif BM, Krell PJ. 2011. Interaction of Autographa californica multiple nucleopolyhedrovirus cathepsin protease progenitor (proV-CATH) with insect baculovirus chitinase as a mechanism for proV-CATH cellular retention. J Virol 85(8):3918-3929.
Hogle JM, Chow M, Filman DJ. 1985. Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229(4720):1358-1365.
Hom LG, Ohkawa T, Trudeau D, Volkman LE. 2002. Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during infected cell death. Virology 296(2):212-218.
Hom LG, Volkman LE. 2000. Autographa californica M nucleopolyhedrovirus chiA is required for processing of V-CATH. Virology 277(1):178-183.
Hu YC, Hsu JT, Huang JH, Ho MS, Ho YC. 2003. Formation of enterovirus-like particle aggregates by recombinant baculoviruses co-expressing P1 and 3CD in insect cells. Biotechnol Lett 25(12):919-925.
Huang CC, Liu CC, Chang YC, Chen CY, Wang ST, Yeh TF. 1999. Neurologic complications in children with enterovirus 71 infection. N Engl J Med 341(13):936-942.
Huang YP, Lin TL, Kuo CY, Lin MW, Yao CY, Liao HW, Hsu LC, Yang CF, Yang JY, Chen PJ and others. 2008. The circulation of subgenogroups B5 and C5 of enterovirus 71 in Taiwan from 2006 to 2007. Virus Res 137(2):206-212.
Hummeler K, Anderson TF, Brown RA. 1962. Identification of poliovirus particles of different antigenicity by specific agglutination as seen in the electron microscope. Virology 16:84-90.
Jacobson MF, Baltimore D. 1968. Morphogenesis of poliovirus. I. Association of the viral RNA with coat protein. J Mol Biol 33(2):369-378.
Jin J, Ma H, Xu L, An D, Sun S, Huang X, Kong W, Jiang C. 2013. Development of a Coxsackievirus A16 neutralization assay based on pseudoviruses for measurement of neutralizing antibody titer in human serum. J Virol Methods 187(2):362-367.
Johansen LK, Morrow CD. 2000. Inherent instability of poliovirus genomes containing two internal ribosome entry site (IRES) elements supports a role for the IRES in encapsidation. J Virol 74(18):8335-8342.
Kaba SA, Salcedo AM, Wafula PO, Vlak JM, van Oers MM. 2004. Development of a chitinase and v-cathepsin negative bacmid for improved integrity of secreted recombinant proteins. J Virol Methods 122(1):113-118.
Koho T, Koivunen MR, Oikarinen S, Kummola L, Makinen S, Mahonen AJ, Sioofy-Khojine A, Marjomaki V, Kazmertsuk A, Junttila I and others. 2014. Coxsackievirus B3 VLPs purified by ion exchange chromatography elicit strong immune responses in mice. Antiviral Res 104:93-101.
Kuge S, Saito I, Nomoto A. 1986. Primary structure of poliovirus defective-interfering particle genomes and possible generation mechanisms of the particles. J Mol Biol 192(3):473-487.
Lee KS, Je YH, Woo SD, Sohn HD, Jin BR. 2006. Production of a cellulase in silkworm larvae using a recombinant Bombyx mori nucleopolyhedrovirus lacking the virus-encoded chitinase and cathepsin genes. Biotechnol Lett 28(9):645-650.
Lee YF, Nomoto A, Detjen BM, Wimmer E. 1977. A protein covalently linked to poliovirus genome RNA. Proc Natl Acad Sci U S A 74(1):59-63.
Lenz P, Day PM, Pang YYS, Frye SA, Jensen PN, Lowy DR, Schiller JT. 2001. Papillomavirus-like particles induce acute activation of dendritic cells. J. Immunol. 166(9):5346-5355.
Li XH, Wang D, Zhou F, Yang HJ, Bhaskar R, Hu JB, Sun CG, Miao YG. 2010. Cloning and expression of a cellulase gene in the silkworm, Bombyx mori by improved Bac-to-Bac/BmNPV baculovirus expression system. Mol Biol Rep 37(8):3721-3728.
Li XH, Wang MX, Zhang P, Hu JB, Sun CG, Liu XJ, Zhou F, Niu YS, Malik FA, Bhaskar R and others. 2011. Heterologous Expression Characteristics of Trichoderma viride Endoglucanase V in the Silkworm, Bombyx mori L. Appl Biochem Biotechnol 165(2):728-736.
Lin YL, Yu CI, Hu YC, Tsai TJ, Kuo YC, Chi WK, Lin AN, Chiang BL. 2012. Enterovirus type 71 neutralizing antibodies in the serum of macaque monkeys immunized with EV71 virus-like particles. Vaccine 30(7):1305-1312.
Liu CC, Chou AH, Lien SP, Lin HY, Liu SJ, Chang JY, Guo MS, Chow YH, Yang WS, Chang KH and others. 2011a. Identification and characterization of a cross-neutralization epitope of Enterovirus 71. Vaccine 29(26):4362-4372.
Liu CC, Guo MS, Lin FH, Hsiao KN, Chang KH, Chou AH, Wang YC, Chen YC, Yang CS, Chong PC. 2011b. Purification and characterization of enterovirus 71 viral particles produced from vero cells grown in a serum-free microcarrier bioreactor system. PLoS One 6(5):e20005.
Liu Y, Wang C, Mueller S, Paul AV, Wimmer E, Jiang P. 2010. Direct interaction between two viral proteins, the nonstructural protein 2C and the capsid protein VP3, is required for enterovirus morphogenesis. PLoS Pathog 6(8):e1001066.
Liu YV, Massare MJ, Barnard DL, Kort T, Nathan M, Wang L, Smith G. 2011c. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV. Vaccine 29(38):6606-6613.
Lokugamage KG, Yoshikawa-Iwata N, Ito N, Watts DM, Wyde PR, Wang N, Newman P, Kent Tseng CT, Peters CJ, Makino S. 2008. Chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (SCoV) S protein protect mice against challenge with SCoV. Vaccine 26(6):797-808.
Lu B, Huang Y, Huang L, Li B, Zheng Z, Chen Z, Chen J, Hu Q, Wang H. 2010. Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice. Immunology 130(2):254-261.
Lundquist RE, Sullivan M, Maizel JV, Jr. 1979. Characterization of a new isolate of poliovirus defective interfering particles. Cell 18(3):759-769.
Luo M, Vriend G, Kamer G, Minor I, Arnold E, Rossmann MG, Boege U, Scraba DG, Duke GM, Palmenberg AC. 1987. The atomic structure of Mengo virus at 3.0 A resolution. Science 235(4785):182-191.
Mateu MG. 1995. Antibody recognization of piconaviruses and escape from neutralization: a structural view. Virus Res. 38:1-24.
McBurney SP, Ross TM. 2009. Human immunodeficiency virus-like particles with consensus envelopes elicited broader cell-mediated peripheral and mucosal immune responses than polyvalent and monovalent Env vaccines. Vaccine 27(32):4337-4349.
Metz SW, Geertsema C, Martina BE, Andrade P, Heldens JG, van Oers MM, Goldbach RW, Vlak JM, Pijlman GP. 2011. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells. Virol J 8:353.
Minor PD. 1992. The molecular biology of poliovaccines. J. Gen. Virol. 73:3065-3077.
Minor PD, Ferguson M, Evans DMA, Almond JW, Icenogle JP. 1986. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J. Gen. Virol. 67:1283-1291.
Molla A, Jang SK, Paul AV, Reuer Q, Wimmer E. 1992. Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus. Nature 356(6366):255-257.
Muir P, Kammerer U, Korn K, Mulders MN, Poyry T, Weissbrich B, Kandolf R, Cleator GM, van Loon AM. 1998. Molecular typing of enteroviruses: current status and future requirements. The European Union Concerted Action on Virus Meningitis and Encephalitis. Clin Microbiol Rev 11(1):202-227.
Nasri D, Bouslama L, Pillet S, Bourlet T, Aouni M, Pozzetto B. 2007. Basic rationale, current methods and future directions for molecular typing of human enterovirus. Expert Rev Mol Diagn 7(4):419-434.
Noad R, Roy P. 2003. Virus-like particles as immunogens. Trends Microbiol 11(9):438-444.
Novak JE, Kirkegaard K. 1991. Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells. J Virol 65(6):3384-3387.
Nugent CI, Johnson KL, Sarnow P, Kirkegaard K. 1999. Functional coupling between replication and packaging of poliovirus replicon RNA. J Virol 73(1):427-435.
O'Reilly D, L M, V L. 1992. Baculovirus expression vecter: a laboratory manual. New York: W.H. Freeman and Co.
Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT. 2008. Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis. J Neuropathol Exp Neurol 67(6):532-542.
Pallansch MA, Roos R. 2006. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. Knipe DM HP, Griffin DE, Lamb RA, Martin MA, Roizman, B SSe, editors. Philadelphia: Lippincott Williams & Wilkins. 839 - 893 p.
Pennock GD, Shoemaker C, Miller LK. 1984. Strong and regulated expression of Escherichia coli beta-galactosidase in insect cells with a baculovirus vector. Mol Cell Biol 4(3):399-406.
Porter DC, Ansardi DC, Morrow CD. 1995. Encapsidation of poliovirus replicons encoding the complete human immunodeficiency virus type 1 gag gene by using a complementation system which provides the P1 capsid protein in trans. J Virol 69(3):1548-1555.
Porter DC, Ansardi DC, Wang J, McPherson S, Moldoveanu Z, Morrow CD. 1998. Demonstration of the specificity of poliovirus encapsidation using a novel replicon which encodes enzymatically active firefly luciferase. Virology 243(1):1-11.
Putnak JR, Phillips BA. 1981. Picornaviral structure and assembly. Microbiol Rev 45(2):287-315.
Ranganathan S, Singh S, Poh CL, Chow VT. 2002. The hand, foot and mouth disease virus capsid: sequence analysis and prediction of antigenic sites from homology modelling. Appl Bioinformatics 1(1):43-52.
Reimann BY, Zell R, Kandolf R. 1991. Mapping of a neutralizing antigenic site of coxsackie B4 by construction of an antigenic chimera. J. Virol. 65:3475-3480.
Rothberg PG, Harris TJ, Nomoto A, Wimmer E. 1978. O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Proc Natl Acad Sci U S A 75(10):4868-4872.
Roy P. 1996. Genetically engineered particulate virus-like structures and their use as vaccine delivery systems. Intervirology 39(1-2):62-71.
Saville GP, Patmanidi AL, Possee RD, King LA. 2004. Deletion of the Autographa californica nucleopolyhedrovirus chitinase KDEL motif and in vitro and in vivo analysis of the modified virus. J Gen Virol 85(Pt 4):821-831.
Seo JK, Kwon SJ, Rao AL. 2012. A physical interaction between viral replicase and capsid protein is required for genome-packaging specificity in an RNA virus. J Virol 86(11):6210-6221.
Sivasamugham LA, Cardosa MJ, Tan WS, Yusoff K. 2006. Recombinant Newcastle Disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits. J Med Virol 78(8):1096-1104.
Smith GE, Summers MD, Fraser MJ. 1983. Production of human beta interferon in insect cells infected with a baculovirus expression vector. Mol Cell Biol 3(12):2156-2165.
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. 2010. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 10(11):778-790.
Stanway G, Brown F, Christian P, Hovi T, Hyypia T, King AMQ, Knowles NJ, Lemon SM, Minor PD, Pallansch MA and others. 2005. Picornaviridae. Fauquet CM MM, Maniloff J, Desselberger U, Ball LA (eds), editor. Amsterdam: Elsevier Academic Press. 757–778 p.
Tan CS, Cardosa MJ. 2007. High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1. Arch Virol 152(6):1069-1073.
Thomas CJ, Brown HL, Hawes CR, Lee BY, Min MK, King LA, Possee RD. 1998. Localization of a baculovirus-induced chitinase in the insect cell endoplasmic reticulum. J Virol 72(12):10207-10212.
Troupin C, Dehee A, Schnuriger A, Vende P, Poncet D, Garbarg-Chenon A. 2010. Rearranged genomic RNA segments offer a new approach to the reverse genetics of rotaviruses. J Virol 84(13):6711-6719.
Visciano ML, Diomede L, Tagliamonte M, Tornesello ML, Asti V, Bomsel M, Buonaguro FM, Lopalco L, Buonaguro L. 2011. Generation of HIV-1 Virus-Like Particles expressing different HIV-1 glycoproteins. Vaccine 29(31):4903-4912.
Wang C, Jiang P, Sand C, Paul AV, Wimmer E. 2012. Alanine scanning of poliovirus 2CATPase reveals new genetic evidence that capsid protein/2CATPase interactions are essential for morphogenesis. J Virol 86(18):9964-9975.
Wetz K, Habermehl KO. 1982. Specific cross-linking of capsid proteins to virus RNA by ultraviolet irradiation of poliovirus. J. Gen. Virol. 59(Pt 2):397-401.
Wong KT, Munisamy B, Ong KC, Kojima H, Noriyo N, Chua KB, Ong BB, Nagashima K. 2008. The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol 67(2):162-169.
Yang L, Song Y, Li X, Huang X, Liu J, Ding H, Zhu P, Zhou P. 2012. HIV-1 Virus Like Particles Produced by Stably Transfected Drosophila S2 cells - a Desirable Vaccine Component. J Virol.
Yao Q, Bu Z, Vzorov A, Yang C, Compans RW. 2003. Virus-like particle and DNA-based candidate AIDS vaccines. Vaccine 21(7-8):638-643.
Yip CC, Lau SK, Zhou B, Zhang MX, Tsoi HW, Chan KH, Chen XC, Woo PC, Yuen KY. 2010. Emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71. Arch Virol 155(9):1413-1424.
Young KR, McBurney SP, Karkhanis LU, Ross TM. 2006. Virus-like particles: designing an effective AIDS vaccine. Methods 40(1):98-117.
Zhang YX, Wei T, Li XY, Yin X, Li YH, Ding JW, Zhou JM, Zhang GZ, Jin Q, Cen S. 2013a. Construction and characterization of an infectious cDNA clone of enterovirus type 71 subgenotype C4. Virus Genes.
Zhang YX, Wei T, Li XY, Yin X, Li YH, Ding JW, Zhou JM, Zhang GZ, Jin Q, Cen S. 2013b. Construction and characterization of an infectious cDNA clone of enterovirus type 71 subgenotype C4. Virus Genes 47(2):235-243.