CVB3 VP1基因真核质粒的构建、表达及对细胞的影响
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摘要
目的：
构建柯萨奇病毒（CVB3）结构蛋白VP1基因的真核质粒pBudCE4.1-VP1，并检测其在HeLa细胞中的表达，研究VP1蛋白对HeLa细胞形态、活性及细胞周期等方面的影响，为探讨CVB3的分子致病机制奠定基础。
方法：
1.质粒pBudCE4.1-VP1构建：抽提CVB3感染的HeLa细胞的总mRNA，RT-PCR扩增VP1基因，经KpnI和BglII双酶切后，克隆于真核载体pBudCE4.1中，酶切鉴定后进行DNA测序验证；
2.质粒pBudCE4.1-VP1表达：将质粒pBudCE4.1-VP1转染HeLa细胞，采用Western blotting和间接免疫荧光技术检测VP1蛋白在HeLa细胞中的表达；
3.质粒pBudCE4.1-VP1对细胞形态和活性的影响：质粒转染HeLa细胞后，倒置显微镜连续观察VP1蛋白对细胞形态的影响，通过MTT法检测HeLa细胞的活性变化；
4.质粒pBudCE4.1-VP1对高尔基体的影响：采用免疫荧光双标技术分析质粒VP1蛋白对细胞高尔基体基质蛋白GM130结构的影响；
5.质粒pBudCE4.1-VP1对细胞周期的影响：以G1/S期为切入点，应用流式细胞仪检测VP1转染后16h、20h、24h、28h、32h等时间点细胞周期的变化。
结果：
1.限制性内切酶酶切和测序结果表明VP1已成功插入pBudCE4.1载体的多克隆位点，其基因序列与CVB3m株（GI:323432）VP1基因序列完全一致。
2. Western blotting和免疫荧光技术结果显示：质粒pBudCE4.1-VP1转染HeLa细胞后能检测到VP1蛋白的表达，且表达量随转染时间的延长而增加；
3.质粒pBudCE4.1-VP1转染HeLa细胞后12h，部分细胞开始变圆；随着转染时间的延长，细胞出现较为明显的病变效应，到转染48h、60h后，几乎未见正常细胞。MTT法结果显示：质粒VP1转染的细胞与对照组细胞相比，OD值明显降低（P＜0.05），且转染时间越长，细胞活性越差；
4.免疫荧光技术分析结果显示：质粒pBudCE4.1-VP1转染HeLa细胞后，随VP1蛋白表达量的增加，细胞蛋白GM130绿色荧光由带状分布趋于弥散，呈散在分布，且荧光强度减弱；
5.细胞周期结果显示：质粒pBudCE4.1-VP1转染HeLa细胞16h、20h、24h、28h、32h后，与空质粒转染对照组G1期细胞相比，VP1转染组G1期细胞分别升高到：58.81%（P＜0.05），57.15%（P＜0.05），54.87%（P＜0.01），55.46%（P＜0.05），56.96%（P＜0.05）。
结论：
1.成功构建CVB3VP1基因真核表达质粒pBudCE4.1-VP1，并能在HeLa细胞中表达；
2. VP1蛋白作用于HeLa细胞后可引起明显的细胞病变效应；
3. VP1蛋白可引起高尔基带断裂，VP1蛋白可能是参与CVB3感染引起高尔基带断裂的主要病毒蛋白之一；
4. VP1蛋白进入细胞后可将细胞周期阻滞在G1期。
Objective:
To construct and identify the recombinant eukaryotic plasmid of CoxsackievirusB3VP1gene, and to detect its expression in HeLa cells. Then observe its effects oncell morphous, cell viability and cell cycle with the aim to investigate the molecularmechanism of CVB3infection.
Methods:
1. Construction of the plasmid pBudCE4.1-VP1: The VP1gene was amplifiedby PCR from a template of total mRNA of CVB3. The amplified DNA wasdirectionally inserted into vector pBudCE4.1. Then the recombinant plasmid wasidentified by restriction endonucleases digestion and sequencing;
2. Expression of the plasmid pBudCE4.1-VP1: The expression of VP1genewas observed by Western blotting and immunofluorescently after transfection;
3. The effection of the plasmid pBudCE4.1-VP1on HeLa cells was detected byMTT assay and observed the change of cell morphology by inverted microscope;
4. To detect the interaction among the CVB3VP1protein and host proteinGM130by confocal microscopy with double immunofluorescent stain aftertransrected;
5. The effection of the plasmid pBudCE4.1-VP1on cell cycle:Cell cycledistribution was detected by flow cytometry after transfeced16h,20h,24h,28h and32h.
Result:
1. The result of restriction endonucleases treatment and sequencing confirmthat VP1gene was successfully inserted into the vector pBudCE4.1in the samesequence to CVB3m type;
2. The reusult of Western blotting and immunofluorescent show that the VP1gene expressed obviously in HeLa cells after transfected and the expression increasedover time;
3. After the VP1transfected into Hela cells12h, a typical cytopathetic effectwas observed in transfected HeLa cells; The reusult of MTT assay show thattransfection of recombinant plasmid pBudCE4.1-VP1can significantly inhibit theproliferation of HeLa cells;
4. The reusult of double immunolabelled GM130and VP1showed that: withthe increased of VP1protein, the GM130was ribbon-like in normal cells and becomedisperse in the transfected cells;
5. Flow cytometry analysis revealed: Compared with the mock transfectedgroup which transfected with vector pBudCE4.1, the proportion of G1phase wasincreased to58.81%(P＜0.05),57.15%(P＜0.05),54.87%(P＜0.01),55.46%(P＜0.05) and56.96%(P＜0.05) at16h,20h,24h,28h and32h post transfection.
Conclusions:
1. The eukaryotic expression plasmid VP1gene of CVB3was successfullyconstructed and express in HeLa cells;
2. The VP1can cause significant cytopathic effect and inhibit the proliferationof HeLa cells;
3. The golgi ribbon was brokendown and the structure of golgi apparatus wasdestroyed after transfection. VP1would be the key structure protein of causing Golgiapparatus destruction in the CVB3infected cells;
4. After tansfecion with pBudCE4.1-VP1, the HeLa cell cycle should be mainlyarrest in G1phage.
构建柯萨奇病毒（CVB3）结构蛋白VP1基因的真核质粒pBudCE4.1-VP1，并检测其在HeLa细胞中的表达，研究VP1蛋白对HeLa细胞形态、活性及细胞周期等方面的影响，为探讨CVB3的分子致病机制奠定基础。
方法：
1.质粒pBudCE4.1-VP1构建：抽提CVB3感染的HeLa细胞的总mRNA，RT-PCR扩增VP1基因，经KpnI和BglII双酶切后，克隆于真核载体pBudCE4.1中，酶切鉴定后进行DNA测序验证；
2.质粒pBudCE4.1-VP1表达：将质粒pBudCE4.1-VP1转染HeLa细胞，采用Western blotting和间接免疫荧光技术检测VP1蛋白在HeLa细胞中的表达；
3.质粒pBudCE4.1-VP1对细胞形态和活性的影响：质粒转染HeLa细胞后，倒置显微镜连续观察VP1蛋白对细胞形态的影响，通过MTT法检测HeLa细胞的活性变化；
4.质粒pBudCE4.1-VP1对高尔基体的影响：采用免疫荧光双标技术分析质粒VP1蛋白对细胞高尔基体基质蛋白GM130结构的影响；
5.质粒pBudCE4.1-VP1对细胞周期的影响：以G1/S期为切入点，应用流式细胞仪检测VP1转染后16h、20h、24h、28h、32h等时间点细胞周期的变化。
结果：
1.限制性内切酶酶切和测序结果表明VP1已成功插入pBudCE4.1载体的多克隆位点，其基因序列与CVB3m株（GI:323432）VP1基因序列完全一致。
2. Western blotting和免疫荧光技术结果显示：质粒pBudCE4.1-VP1转染HeLa细胞后能检测到VP1蛋白的表达，且表达量随转染时间的延长而增加；
3.质粒pBudCE4.1-VP1转染HeLa细胞后12h，部分细胞开始变圆；随着转染时间的延长，细胞出现较为明显的病变效应，到转染48h、60h后，几乎未见正常细胞。MTT法结果显示：质粒VP1转染的细胞与对照组细胞相比，OD值明显降低（P＜0.05），且转染时间越长，细胞活性越差；
4.免疫荧光技术分析结果显示：质粒pBudCE4.1-VP1转染HeLa细胞后，随VP1蛋白表达量的增加，细胞蛋白GM130绿色荧光由带状分布趋于弥散，呈散在分布，且荧光强度减弱；
5.细胞周期结果显示：质粒pBudCE4.1-VP1转染HeLa细胞16h、20h、24h、28h、32h后，与空质粒转染对照组G1期细胞相比，VP1转染组G1期细胞分别升高到：58.81%（P＜0.05），57.15%（P＜0.05），54.87%（P＜0.01），55.46%（P＜0.05），56.96%（P＜0.05）。
结论：
1.成功构建CVB3VP1基因真核表达质粒pBudCE4.1-VP1，并能在HeLa细胞中表达；
2. VP1蛋白作用于HeLa细胞后可引起明显的细胞病变效应；
3. VP1蛋白可引起高尔基带断裂，VP1蛋白可能是参与CVB3感染引起高尔基带断裂的主要病毒蛋白之一；
4. VP1蛋白进入细胞后可将细胞周期阻滞在G1期。
Objective:
To construct and identify the recombinant eukaryotic plasmid of CoxsackievirusB3VP1gene, and to detect its expression in HeLa cells. Then observe its effects oncell morphous, cell viability and cell cycle with the aim to investigate the molecularmechanism of CVB3infection.
Methods:
1. Construction of the plasmid pBudCE4.1-VP1: The VP1gene was amplifiedby PCR from a template of total mRNA of CVB3. The amplified DNA wasdirectionally inserted into vector pBudCE4.1. Then the recombinant plasmid wasidentified by restriction endonucleases digestion and sequencing;
2. Expression of the plasmid pBudCE4.1-VP1: The expression of VP1genewas observed by Western blotting and immunofluorescently after transfection;
3. The effection of the plasmid pBudCE4.1-VP1on HeLa cells was detected byMTT assay and observed the change of cell morphology by inverted microscope;
4. To detect the interaction among the CVB3VP1protein and host proteinGM130by confocal microscopy with double immunofluorescent stain aftertransrected;
5. The effection of the plasmid pBudCE4.1-VP1on cell cycle:Cell cycledistribution was detected by flow cytometry after transfeced16h,20h,24h,28h and32h.
Result:
1. The result of restriction endonucleases treatment and sequencing confirmthat VP1gene was successfully inserted into the vector pBudCE4.1in the samesequence to CVB3m type;
2. The reusult of Western blotting and immunofluorescent show that the VP1gene expressed obviously in HeLa cells after transfected and the expression increasedover time;
3. After the VP1transfected into Hela cells12h, a typical cytopathetic effectwas observed in transfected HeLa cells; The reusult of MTT assay show thattransfection of recombinant plasmid pBudCE4.1-VP1can significantly inhibit theproliferation of HeLa cells;
4. The reusult of double immunolabelled GM130and VP1showed that: withthe increased of VP1protein, the GM130was ribbon-like in normal cells and becomedisperse in the transfected cells;
5. Flow cytometry analysis revealed: Compared with the mock transfectedgroup which transfected with vector pBudCE4.1, the proportion of G1phase wasincreased to58.81%(P＜0.05),57.15%(P＜0.05),54.87%(P＜0.01),55.46%(P＜0.05) and56.96%(P＜0.05) at16h,20h,24h,28h and32h post transfection.
Conclusions:
1. The eukaryotic expression plasmid VP1gene of CVB3was successfullyconstructed and express in HeLa cells;
2. The VP1can cause significant cytopathic effect and inhibit the proliferationof HeLa cells;
3. The golgi ribbon was brokendown and the structure of golgi apparatus wasdestroyed after transfection. VP1would be the key structure protein of causing Golgiapparatus destruction in the CVB3infected cells;
4. After tansfecion with pBudCE4.1-VP1, the HeLa cell cycle should be mainlyarrest in G1phage.
引文
[1] Dalldorf G, Sickles GM. An Unidentified, Filtrable Agent Isolated From the Feces ofChildren With Paralysis. Science1948Jul16;108(2794):61-62.
[2] Melnick JL, Shaw EW, Curnen EC. A Virus Isolated from Patients Diagnosed asNon-Paralytic Poliomyelitis or Aseptic Meningitis. Exp Biol Med1949July1,1949;71(3):344-349.
[3]闻玉梅主编.现代医学微生物学（第一版）1999:1205-1244.
[4] Fujimoto T, Iizuka S, Enomoto M, Abe K, Yamashita K, Hanaoka N, et al. Hand, foot, andmouth disease caused by coxsackievirus A6, Japan, Emerg Infect Dis2011Feb;18(2):337-339.
[5] Han JF, Jiang T, Fan XL, Yang LM, Yu M, Cao RY, et al. Recombination of humancoxsackievirus B5in hand, foot, and mouth disease patients, China. Emerg Infect Dis2012Feb;18(2):351-353.
[6] Yun S-H, Lee WG, Kim Y-C, Ju E-S, Lim B-K, Choi J-O, et al. Antiviral Activity ofCoxsackievirus B33C Protease Inhibitor in Experimental Murine Myocarditis. The Journalof Infectious Disease2012February1;205(3):491-497.
[7] Freeman R, McMahon MJ. Acute pancreatitis and serological evidence of infection withMycoplasma pneumoniae. Gut1978May;19(5):367-370.
[8] Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattre P, et al. Persistent infectionof human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesisin beta cells. J Virol2000Nov;74(21):10153-10164.
[9] Wong AH, Lau CS, Cheng PK, Ng AY, Lim WW. Coxsackievirus B3-associated asepticmeningitis: an emerging infection in Hong Kong. J Med Virol2011Mar;83(3):483-489.
[10] Huber S, Ramsingh AI. Coxsackievirus-induced pancreatitis. Viral Immunol2004;17(3):358-369.
[11] Gottenberg JE, Pallier C, Ittah M, Lavie F, Miceli-Richard C, Sellam J, et al. Failure toconfirm coxsackievirus infection in primary Sjogren's syndrome. Arthritis Rheum2006Jun;54(6):2026-2028.
[12] Rickels MR, Schutta MH, Markmann JF, Barker CF, Naji A, Teff KL.{beta}-Cell FunctionFollowing Human Islet Transplantation for Type1Diabetes. Diabetes2005January1,2005;54(1):100-106.
[13] Jaidane H, Hober D. Role of coxsackievirus B4in the pathogenesis of type1diabetes.Diabetes Metab2008Dec;34(6Pt1):537-548.
[14] Jaidane H, Sane F, Gharbi J, Aouni M, Romond MB, Hober D. Coxsackievirus B4and type1diabetes pathogenesis: contribution of animal models. Diabetes Metab Res Rev2009Oct;25(7):591-603.
[15] Lindberg AM, Stalhandske PO, Pettersson U. Genome of coxsackievirus B3. Virology1987Jan;156(1):50-63.
[16] Beck MA, Shi Q, Morris VC, Levander OA. Rapid genomic evolution of a non-virulentcoxsackievirus B3in selenium-deficient mice results in selection of identical virulent isolates.Nat Med1995May;1(5):433-436.
[17] Stadnick E, Dan M, Sadeghi A, Chantler JK. Attenuating mutations in coxsackievirus B3map to a conformational epitope that comprises the puff region of VP2and the knob of VP3.J Virol2004Dec;78(24):13987-14002.
[18] Smith CP, Clements GB, Riding MH, Collins P, Bottazzo GF, Taylor KW. Simultaneousonset of type1diabetes mellitus in identical infant twins with enterovirus infection. DiabetMed1998Jun;15(6):515-517.
[19] Muckelbauer JK, Kremer M, Minor I, Tong L, Zlotnick A, Johnson JE, et al. Structuredetermination of coxsackievirus B3to3.5A resolution. Acta Crystallogr D Biol Crystallogr1995Nov1;51(Pt6):871-887.
[20] Wunder T, Schumacher U, Friedrich RE. Coxsackie adenovirus receptor expression incarcinomas of the head and neck. Anticancer Res2012Mar;32(3):1057-1062.
[21] Kasman L, Onicescu G, Voelkel-Johnson C. Histone deacetylase inhibitors restore cellsurface expression of the coxsackie adenovirus receptor and enhance CMV promoter activityin castration-resistant prostate cancer cells. Prostate Cancer;2012:137-163.
[22] Tatrai E, Bedi K, Kovalszky I, Hartyanszky I, Laszik A, Acsady G, et al. No mutation buthigh mRNA expression of Coxsackie-Adenovirus Receptor was observed in both dilated andischemic cardiomyopathy. Forensic Sci Int2011Oct10;212(1-3):47-50.
[23] Kunin CM. Cellular Susceptibility to Enteroviruses. Bacteriol Rev1964Dec;28:382-390.
[24] Knowlton KU, Jeon ES, Berkley N, Wessely R, Huber S. A mutation in the puff region ofVP2attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant ofcoxsackievirus B3. J Virol1996Nov;70(11):7811-7818.
[25] van Kuppeveld FJ, van den Hurk PJ, Zoll J, Galama JM, Melchers WJ. Mutagenesis of thecoxsackie B3virus2B/2C cleavage site: determinants of processing efficiency and effects onviral replication. J Virol1996Nov;70(11):7632-7640.
[26] Moncorge O, Mura M, Barclay WS. Evidence for avian and human host cell factors thataffect the activity of influenza virus polymerase. J Virol2010Oct;84(19):9978-9986.
[27] Kinchington PR, Goins WF. Varicella zoster virus-induced pain and post-herpetic neuralgiain the human host and in rodent animal models. J Neurovirol2011Dec;17(6):590-599.
[28] Muckelbauer JK, Kremer M, Minor I, Diana G, Dutko FJ, Groarke J, et al. The structure ofcoxsackievirus B3at3.5A resolution. Structure1995Jul15;3(7):653-667.
[29] Liu GX, Lan JM, Chuai X, Gao ZY, Jin YH, Zhang YH, et al. Immune effects of fourcoxsackievirus B3VP1DNA fusion vaccines in mice. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi2010Feb;26(2):103-106.
[30] Yan LJ, Gao ZY, Li J, Lan JM, Jin YH, Xie LX, et al. Study on combined immunization ofrAd/MDC-VP1and pcDNA3/MDC-VP1against Coxsackievirus B3challenge in mice. XiBao Yu Fen Zi Mian Yi Xue Za Zhi2012Mar;28(3):228-231.
[31] Bayliss J, Harrison E, McLean CA. Progressive multifocal leukoencephalopathydevelopment is associated with mutations in JC virus capsid protein VP1that change thereceptor specificity of the virus. J Infect Dis2011Nov15;204(10):1643-1644.
[32] Zhong Z, Shi S, Han J, Zhang Z, Sun X. Anionic liposomes increase the efficiency ofadenovirus-mediated gene transfer to coxsackie-adenovirus receptor deficient cells. MolPharm2009Feb1;7(1):105-115.
[33] Yuen S, Smith J, Caruso L, Balan M, Opavsky MA. The coxsackie-adenovirus receptorinduces an inflammatory cardiomyopathy independent of viral infection. J Mol Cell Cardiol2011May;50(5):826-840.
[34] Shi Y, Fukuoka M, Li G, Liu Y, Chen M, Konviser M, et al. Regulatory T cells protect miceagainst coxsackievirus-induced myocarditis through the transforming growth factorbeta-coxsackie-adenovirus receptor pathway. Circulation2010Jun22;121(24):2624-2634.
[35] Dietel M, Hafner N, Jansen L, Durst M, Runnebaum IB. Novel splice variant CAR4/6of thecoxsackie adenovirus receptor is differentially expressed in cervical carcinogenesis. J MolMed (Berl)2011Jun;89(6):621-630.
[36] Caruso L, Yuen S, Smith J, Husain M, Opavsky MA. Cardiomyocyte-targeted overexpres-sion of the coxsackie-adenovirus receptor causes a cardiomyopathy in association withbeta-catenin signaling. J Mol Cell Cardiol2010Jun;48(6):1194-1205.
[37] Wen C, Gao ZY, Lan JM, Yan LJ, Chuai X, Li J, et al. The effects of inoculation route andadjuvant type on the immunizing potency of CVB3VP1protein. Xi Bao Yu Fen Zi Mian YiXue Za Zhi2011Oct;27(10):1086-1089.
[38] Nikolova I, Galabov AS, Petkova R, Chakarov S, Atanasov B. Disoxaril mutants of Coxsack-ievirus B1: phenotypic characteristics and analysis of the target VP1gene. Z Naturforsch C2011Nov-Dec;66(11-12):627-636.
[39] Wu X, Zhao T, Tian Y.[A bivalent VP1gene vaccine against Coxsackie virus B1/B3].Zhonghua Yi Xue Za Zhi2001Apr25;81(8):480-484.
[40] Nozawa K, Fritzler MJ, Ikeda K, Takasaki Y, Satoh M, Chan EK. Differential anti-Golgicomplex autoantibody production following murine lactate dehydrogenase-elevating virusinfection. Immunopharmacol Immunotoxicol2008;30(1):13-25.
[41] Desai P, Sexton GL, Huang E, Person S. Localization of herpes simplex virus type1UL37inthe Golgi complex requires UL36but not capsid structures. J Virol2008Nov;82(22):11354-11361.
[42] Hambleton S, Gershon M, Gershon A. The role of the trans-Golgi network in varicella zostervirus biology. Cell Mol Life Sci2004December1,2004;61(24):3047-3056.
[43] Lontok E, Corse E, Machamer CE. Intracellular Targeting Signals Contribute to Localizationof Coronavirus Spike Proteins near the Virus Assembly Site. J Virol2004June1,2004;78(11):5913-5922.
[44] Bertolotti-Ciarlet A, Smith J, Strecker K, Paragas J, Altamura LA, McFalls JM, et al. CellularLocalization and Antigenic Characterization of Crimean-Congo Hemorrhagic Fever VirusGlycoproteins. J Virol2005May15,2005;79(10):6152-6161.
[45] Jarvis MA, Jones TR, Drummond DD, Smith PP, Britt WJ, Nelson JA, et al. Phosphorylationof Human Cytomegalovirus Glycoprotein B (gB) at the Acidic Cluster Casein Kinase2Site(Ser900) Is Required for Localization of gB to the trans-Golgi Network and Efficient VirusReplication. J Virol2004January1,2004;78(1):285-293.
[46] Karabekian Z, Hanson LK, Slater JS, Krishna NK, Bolin LL, Kerry JA, et al. ComplexFormation among Murine Cytomegalovirus US22Proteins Encoded by Genes M139, M140,and M141. J Virol2005March15,2005;79(6):3525-3535.
[47] Hasan M, Krmpotic A, Ruzsics Z, Bubic I, Lenac T, Halenius A, et al. SelectiveDown-Regulation of the NKG2D Ligand H60by Mouse Cytomegalovirus m155Glycoprotein. J Virol2005March1,2005;79(5):2920-2930.
[48]刘发娣. CVB3对Hela细胞高尔基体及其细胞周期的影响;2009.
[49] Puthenveedu MA, Bachert C, Puri S, Lanni F, Linstedt AD. GM130and GRASP65-dependent lateral cisternal fusion allows uniform Golgi-enzyme distribution. Nat Cell Biol2006Mar;8(3):238-248.
[50] Feinstein TN, Linstedt AD. GRASP55regulates Golgi ribbon formation. Mol Biol Cell2008Jul;19(7):2696-2707.
[51] Nascimento R, Costa H, Parkhouse RM. Virus manipulation of cell cycle. Protoplasma2011Oct11.
[52] Kannan RP, Hensley LL, Evers LE, Lemon SM, McGivern DR. Hepatitis C virus infectioncauses cell cycle arrest at the level of initiation of mitosis. J Virol2011Aug;85(16):7989-8001.
[53] Maalouf K, Baydoun E, Rizk S. Kefir induces cell-cycle arrest and apoptosis inHTLV-1-negative malignant T-lymphocytes. Cancer Manag Res;2011March;3:39-47.
[54] Zhang SM, Song M, Yang TY, Fan R, Liu XD, Zhou PK. HIV-1Tat impairs cell cyclecontrol by targeting the Tip60, Plk1and cyclin B1ternary complex. Cell Cycle2012Mar15;11(6).
[55] Luo H, Zhang J, Dastvan F, Yanagawa B, Reidy MA, Zhang HM, et al. Ubiquitin-dependentproteolysis of cyclin D1is associated with coxsackievirus-induced cell growth arrest. J Virol2003Jan;77(1):1-9.
[56] Feuer R, Mena I, Pagarigan R, Slifka MK, Whitton JL. Cell cycle status affectscoxsackievirus replication, persistence, and reactivation in vitro. J Virol2002May;76(9):4430-4440.
[57] Feuer R, Mena I, Pagarigan RR, Hassett DE, Whitton JL. Coxsackievirus replication and thecell cycle: a potential regulatory mechanism for viral persistence/latency. Med MicrobiolImmunol2004May;193(2-3):83-90.
[58]黄孝天.柯萨奇B3病毒VP1与人细胞蛋白直接作用的研究.上海交通大学2005.
[59] Barr FA, Nakamura N, Warren G. Mapping the interaction between GRASP65and GM130,components of a protein complex involved in the stacking of Golgi cisternae. EMBO J1998Jun15;17(12):3258-3268.
[60] Mistchenko AS, Viegas M, Latta MP, Barrero PR. Molecular and epidemiologic analysis ofenterovirus B neurological infection in Argentine children. J Clin Virol2006Dec;37(4):293-299.
[61] Haarmann CM, Schwimmbeck PL, Mertens T, Schultheiss HP, Strauer BE. Identification ofserotype-specific and nonserotype-specific B-cell epitopes of coxsackie B virus usingsynthetic peptides. Virology1994May1;200(2):381-389.
[62] Boshart M, Weber F, Jahn G, Dorsch-Hasler K, Fleckenstein B, Schaffner W. A very strongenhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell1985Jun;41(2):521-530.
[63] Persic L, Roberts A, Wilton J, Cattaneo A, Bradbury A, Hoogenboom HR. An integratedvector system for the eukaryotic expression of antibodies or their fragments after selectionfrom phage display libraries. Gene1997Mar10;187(1):9-18.
[64] Romano M, Roupie V, Hamard M, Huygen K. Evaluation of the immunogenicity ofpBudCE4.1plasmids encoding mycolyl-transferase Ag85A and phosphate transport receptorPstS-3from Mycobacterium tuberculosis. Vaccine2006May22;24(21):4640-4643.
[65] Hou WR, Xie SN, Lu JL, Xi W, Luo X, Xiang M. Recombination of RegIII-proinsulin-pBudCE4.1plasmid and its therapeutic effect on STZ-induced type1diabetes mellitus. YaoXue Xue Bao2011Aug;45(8):987-994.
[66] Moeini H, Omar AR, Rahim RA, Yusoff K. Improving the potency of DNA vaccine againstchicken anemia virus (CAV) by fusing VP1protein of CAV to Marek's Disease Virus (MDV)type-1VP22protein. Virol J;2011March;8:119.
[67] Zhang HM, Ye X, Su Y, Yuan J, Liu Z, Stein DA, et al. Coxsackievirus B3infection activatesthe unfolded protein response and induces apoptosis through downregulation of p58IPK andactivation of CHOP and SREBP1. J Virol Sep;84(17):8446-8459.
[68] Esfandiarei M, McManus BM. Molecular biology and pathogenesis of viral myocarditis.Annu Rev Pathol2008;3:127-155.
[69] Bisel B, Wang Y, Wei JH, Xiang Y, Tang D, Miron-Mendoza M, et al. ERK regulates Golgiand centrosome orientation towards the leading edge through GRASP65. J Cell Biol2008Sep8;182(5):837-843.
[70] Tang D, Yuan H, Wang Y. The role of GRASP65in Golgi cisternal stacking and cell cycleprogression. Traffic2010Jun;11(6):827-842.
[71] Xiang Y, Wang Y. GRASP55and GRASP65play complementary and essential roles in Golgicisternal stacking. J Cell Biol2010Jan25;188(2):237-251.
[72]徐秋芳.宿主蛋白GM130在CVB3病毒性胰腺炎中的分子作用机制研究.2010.
[73] Wessels E, Duijsings D, Lanke KH, Melchers WJ, Jackson CL, van Kuppeveld FJ.Molecular determinants of the interaction between coxsackievirus protein3A and guaninenucleotide exchange factor GBF1. J Virol2007May;81(10):5238-5245.
[74] de Jong AS, Visch HJ, de Mattia F, van Dommelen MM, Swarts HG, Luyten T, et al. Thecoxsackievirus2B protein increases efflux of ions from the endoplasmic reticulum and Golgi,thereby inhibiting protein trafficking through the Golgi. J Biol Chem2006May19;281(20):14144-14150.
[75] Yao HL, Xiao ZH, Ren HY, Han JS, Liu ZW.[Study on inhibition of coxsackievirus B3infection in HeLa cell by short interfering RNA targeting2B protein]. Bing Du Xue Bao2007Jul;23(4):276-281.
[76] Marra P, Salvatore L, Mironov A, Jr., Di Campli A, Di Tullio G, Trucco A, et al. Thebiogenesis of the Golgi ribbon: the roles of membrane input from the ER and of GM130.Mol Biol Cell2007May;18(5):1595-1608.
[77] Feuer R, Whitton JL. Preferential coxsackievirus replication in proliferating/activated cells:implications for virus tropism, persistence, and pathogenesis. Curr Top Microbiol Immunol2008;323:149-173.
[78] Hobbs WE,2nd, DeLuca NA. Perturbation of cell cycle progression and cellular geneexpression as a function of herpes simplex virus ICP0. J Virol1999Oct;73(10):8245-8255.
[79] Lu M, Shenk T. Human cytomegalovirus UL69protein induces cells to accumulate in G1phase of the cell cycle. J Virol1999Jan;73(1):676-683.
[80] Barnitz RA, Chaigne-Delalande B, Bolton DL, Lenardo MJ. Exposed hydrophobic residuesin human immunodeficiency virus type1Vpr helix-1are important for cell cycle arrest andcell death. PLoS One2011Sep;6(9): e24924.
[81] Li L, Gu B, Zhou F, Chi J, Wang F, Peng G, et al. Human herpesvirus6suppresses T cellproliferation through induction of cell cycle arrest in infected cells in the G2/M phase. J Virol2011Jul;85(13):6774-6783.
[82] Gatza ML, Chandhasin C, Ducu RI, Marriott SJ. Impact of transforming viruses on cellularmutagenesis, genome stability, and cellular transformation. Environ Mol Mutagen2005Mar-Apr;45(2-3):304-325.
[83] Baydoun HH, Pancewicz J, Bai X, Nicot C. HTLV-I p30inhibits multiple S phase entrycheckpoints, decreases cyclin E-CDK2interactions and delays cell cycle progression. MolCancer2010;9:302.
[84] Ohkawa K, Ishida H, Nakanishi F, Hosui A, Ueda K, Takehara T, et al. Hepatitis C virus corefunctions as a suppressor of cyclin-dependent kinase-activating kinase and impairs cell cycleprogression. J Biol Chem2004Mar19;279(12):11719-11726.
[85]王灵枢,刘晶星,朱莉.柯萨奇B3病毒结构和非结构蛋白DNA疫苗诱导小鼠产生免疫应答的研究.中华微生物学和免疫学杂志2001;21(1):46-49.
[86] Ding FX, Wang F, Lu YM, Li K, Wang KH, He XW, et al. Multiepitope peptide-loadedvirus-like particles as a vaccine against hepatitis B virus-related hepatocellular carcinoma.Hepatology2009May;49(5):1492-1502.
[87] Goon P, Sonnex C, Jani P, Stanley M, Sudhoff H. Recurrent respiratory papillomatosis: anoverview of current thinking and treatment. Eur Arch Otorhinolaryngol2008Feb;265(2):147-151.
[88] Zhang L, Parham NJ, Zhang F, Aasa-Chapman M, Gould EA, Zhang H. Vaccination withcoxsackievirus B3virus-like particles elicits humoral immune response and protects miceagainst myocarditis. Vaccine2012Mar16;30(13):2301-2308.
[89] Chung YC, Ho MS, Wu JC, Chen WJ, Huang JH, Chou ST, et al. Immunization withvirus-like particles of enterovirus71elicits potent immune responses and protects miceagainst lethal challenge. Vaccine2008Mar28;26(15):1855-1862.
[90] Kui X, Sun M, Xie T, Wang W, Jiang L, Yan M, et al. The expression, purification, andimmunogenicity of a new chimeric virus-like particle. Viral Immunol2009Feb;22(1):49-56.
[91] Urakawa T, Ferguson M, Minor PD, Cooper J, Sullivan M, Almond JW, et al. Synthesis ofimmunogenic, but non-infectious, poliovirus particles in insect cells by a baculovirusexpression vector. J Gen Virol1989Jun;70(Pt6):1453-1463.
[92] Hiscox JA. RNA viruses: hijacking the dynamic nucleolus. Nat Rev Microbiol2007Feb;5(2):119-127.
[93] Zhou G, Doci CL, Lingen MW. Identification and functional analysis of NOL7nuclear andnucleolar localization signals. BMC Cell Biol2010;11(74):1471-2121
[94] Vihinen-Ranta M, Wang D, Weichert WS, Parrish CR. The VP1N-terminal sequence ofcanine parvovirus affects nuclear transport of capsids and efficient cell infection. J Virol2002Feb;76(4):1884-1891.
[95] Lombardo E, Ramirez JC, Garcia J, Almendral JM. Complementary roles of multiple nucleartargeting signals in the capsid proteins of the parvovirus minute virus of mice duringassembly and onset of infection. J Virol2002Jul;76(14):7049-7059.
[96] Lombardo E, Ramirez JC, Agbandje-McKenna M, Almendral JM. A beta-stranded motifdrives capsid protein oligomers of the parvovirus minute virus of mice into the nucleus forviral assembly. J Virol2000Apr;74(8):3804-3814.
[1] O. Jenkins, J. D. Booth, P. D. Minor and J. W. Almond, The Complete Nucleotide Sequenceof Coxsackievirus B4and Its Comparison to Other Members of the Picornaviridae, J. Gen.Virol.,68(1987), pp.1835-1848.
[2] D. D. Banker and J. L. Melnick, Isolation of Coxsackie virus (C virus) from North AlaskanEskimos, Am J Hyg,54(1951), pp.383-90.
[3] I. Zajac and R. L. Crowell, Effect of Enzymes on the Interaction of Enteroviruses withLiving Hela Cells, J Bacteriol,89(1965), pp.574-82.
[4] M. R. Rickels, M. H. Schutta, J. F. Markmann, C. F. Barker, A. Naji and K. L. Teff,{beta}-Cell Function Following Human Islet Transplantation for Type1Diabetes, Diabetes,54(2005), pp.100-106.
[5] C. Cordon-Cardo and C. Prives, At the Crossroads of Inflammation and Tumorigenesis, J.Exp. Med.,190(1999), pp.1367-1370.
[6] K. Klingel, S. Stephan, M. Sauter, R. Zell, B. M. McManus, B. Bultmann and R. Kandolf,Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets,J Virol,70(1996), pp.8888-95.
[7] R. Crowell and B. Landau, A short history and introductory background on thecoxsackieviruses of group B, Curr Top Microbiol Immunol,223(1997), pp.1-11.
[8] R. Freeman and M. J. McMahon, Acute pancreatitis and serological evidence of infectionwith Mycoplasma pneumoniae, Gut,19(1978), pp.367-70.
[9] T. Szopa, P. Titchener, N. Portwood and K. Taylor, Diabetes mellitus due to viruses--somerecent developments, Diabetologia,36(1993), pp.687-95.
[10] S. Tracy, K. M. Drescher, N. M. Chapman, K. S. Kim, S. D. Carson, S. Pirruccello, P. H.Lane, J. R. Romero and J. S. Leser, Toward testing the hypothesis that group Bcoxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabeticmice with CVB markedly lowers diabetes incidence, J Virol,76(2002), pp.12097-111.
[11] H. Champsaur, G. Bottazzo, J. Bertrams, R. Assan and C. Bach, Virologic, immunologic, andgenetic factors in insulin-dependent diabetes mellitus, J Pediatr,100(1982), pp.15-20.
[12] J. Yoon, M. Austin, T. Onodera and A. Notkins, Isolation of a virus from the pancreas of achild with diabetic ketoacidosis, N. Engl. J. Med.,300(1979), pp.1173-1179.
[13] Reviews and Notes: Gastroenterology: Acute Pancreatitis: Diagnosis and Therapy, AnnIntern Med,120(1994), pp.352-d-.
[14] P. Lankisch, S. Burchard-Reckert, M. Petersen, D. Lehnick, C. Schirren, H. Kohler, F.Stockmann, H. Peiper and W. Creutzfeldt, Morbidity and mortality in602patients with acutepancreatitis seen between the years1980-1994, Z Gastroenterol,34(1996), pp.371-7.
[15] B. Arnesjo, T. Eden, I. Ihse, E. Nordenfelt and B. Ursing, Enterovirus infections in acutepancreatitis-a possible etiological connection, Scand J Gastroenterol,11(1976), pp.645-9.
[16] P. Capner, R. Lendrum, D. J. Jeffries and G. Walker, Viral antibody studies in pancreaticdisease, Gut,16(1975), pp.866-70.
[17] Z. Ozsvar, J. Deak and A. Pap, Possible role of Coxsackie-B virus infection in pancreatitis,Int J Pancreatol,11(1992), pp.105-8.
[18] D. A. Bass, Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophildynamics during acute inflammation, J Clin Invest,56(1975), pp.870-9.
[19] A. I. Ramsingh, Coxsackieviruses and pancreatitis, Front Biosci,2(1997), pp. e53-62.
[20] A. I. Ramsingh, W. T. Lee, D. N. Collins and L. E. Armstrong, Differential recruitment of Band T cells in coxsackievirus B4-induced pancreatitis is influenced by a capsid protein, JVirol,71(1997), pp.8690-7.
[21] S. E. Ostrowski, A. A. Reilly, D. N. Collins and A. I. Ramsingh, Progression or resolution ofcoxsackievirus B4-induced pancreatitis: a genomic analysis, J Virol,78(2004), pp.8229-37.
[22] V. Ramiya, M. Maraist, K. Arfors, D. Schatz, A. Peck and J. Cornelius, Reversal ofinsulin-dependent diabetes using islets generated in vitro from pancreatic stem cells, NatMed,6(2000), pp.278-82.
[23] H. Elsasser, G. Adler and H. Kern, Time course and cellular source of pancreatic regenerationfollowing acute pancreatitis in the rat, Pancreas,1(1986), pp.421-9.
[24] S. Bonner-Weir, L. Baxter, G. Schuppin and F. Smith, A second pathway for regeneration ofadult exocrine and endocrine pancreas. A possible recapitulation of embryonic development,Diabetes,42(1993), pp.1715-1720.
[25] M. Caggana, P. Chan and A. Ramsingh, Identification of a single amino acid residue in thecapsid protein VP1of coxsackievirus B4that determines the virulent phenotype, J. Virol.,67(1993), pp.4797-4803.
[26] D. M. Potvin, D. W. Metzger, W. T. Lee, D. N. Collins and A. I. Ramsingh, Exogenousinterleukin-12protects against lethal infection with coxsackievirus B4, J Virol,77(2003), pp.8272-9.
[27] A. Ramsingh, J. Slack, J. Silkworth and A. Hixson, Severity of disease induced by apancreatropic Coxsackie B4virus correlates with the H-2Kq locus of the majorhistocompatibility complex, Virus Res,14(1989), pp.347-58.
[28] S. Tracy, K. Hofling, S. Pirruccello, P. H. Lane, S. M. Reyna and C. J. Gauntt, Group Bcoxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypesin mice, J Med Virol,62(2000), pp.70-81.
[29] D. Serreze, E. Ottendorfer, T. Ellis, C. Gauntt and M. Atkinson, Acceleration of type1diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactiveT-cells in pancreatic islets, Diabetes,49(2000), pp.708-711.
[30] R. Blay, K. Simpson, K. Leslie and S. Huber, Coxsackievirus-induced disease. CD4+cellsinitiate both myocarditis and pancreatitis in DBA/2mice, Am J Pathol,135(1989), pp.899-907.
[31] A. Henke, H. Launhardt, K. Klement, A. Stelzner, R. Zell and T. Munder, Apoptosis inCoxsackievirus B3-Caused Diseases: Interaction between the Capsid Protein VP2and theProapoptotic Protein Siva, J. Virol.,74(2000), pp.4284-4290.
[32] B. Jacobs and J. Langland, When two strands are better than one: the mediators andmodulators of the cellular responses to double-stranded RNA, Virology,219(1996), pp.339-49.
[33] K. L. Peters, H. L. Smith, G. R. Stark and G. C. Sen, IRF-3-dependent, NFkappa B-andJNK-independent activation of the561and IFN-beta genes in response to double-strandedRNA, PNAS,99(2002), pp.6322-6327.
[34] J. C. Castelli, B. A. Hassel, K. A. Wood, X.-L. Li, K. Amemiya, M. C. Dalakas, P. F.Torrence and R. J. Youle, A Study of the Interferon Antiviral Mechanism: ApoptosisActivation by the2-5A System, J. Exp. Med.,186(1997), pp.967-972.
[35] K. V. S. Prasad, Z. Ao, Y. Yoon, M. X. Wu, M. Rizk, S. Jacquot and S. F. Schlossman, CD27,a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, aproapoptotic protein, PNAS,94(1997), pp.6346-6351.
[36] G. Geiss, G. Jin, J. Guo, R. Bumgarner, M. G. Katze and G. C. Sen, A Comprehensive Viewof Regulation of Gene Expression by Double-stranded RNA-mediated Cell Signaling, J. Biol.Chem.,276(2001), pp.30178-30182.
[37] A. Kumar, J. Haque, J. Lacoste, J. Hiscott and B. Williams, Double-Stranded RNA-Dependent Protein Kinase Activates Transcription Factor NF-{kappa}B by PhosphorylatingI{kappa}B, PNAS,91(1994), pp.6288-6292.
[38] C. Lowenstein, S. Hill, A. Lafond-Walker, J. Wu, G. Allen, M. Landavere, N. Rose and A.Herskowitz, Nitric oxide inhibits viral replication in murine myocarditis, J Clin Invest,97(1996), pp.1837-43.
[39] W. Fiers, R. Beyaert, E. Boone, S. Cornelis, W. Declercq, E. Decoster, G. Denecker, B.Depuydt, D. De Valck, G. De Wilde, V. Goossens, J. Grooten, G. Haegeman, K. Heyninck, L.Penning, S. Plaisance, K. Vancompernolle, W. Van Criekinge, P. Vandenabeele, W. VandenBerghe, M. Van de Craen, V. Vandevoorde and D. Vercammen, TNF-induced intracellularsignaling leading to gene induction or to cytotoxicity by necrosis or by apoptosis, J Inflamm,47(1995), pp.67-75.
[40] G. L. Freeman, J. T. Colston, M. Zabalgoitia and B. Chandrasekar, Contractile depression andexpression of proinflammatory cytokines and iNOS in viral myocarditis, Am J Physiol HeartCirc Physiol,274(1998), pp. H249-258.
[41] C. Badorff, G. Lee, B. Lamphear, M. Martone, K. Campbell, R. Rhoads and K. Knowlton,Enteroviral protease2A cleaves dystrophin: evidence of cytoskeletal disruption in anacquired cardiomyopathy, Nat Med,5(1999), pp.320-6.
[42] A. Theofilopoulos, The basis of autoimmunity: Part I. Mechanisms of aberrantself-recognition, Immunol Today,16(1995), pp.90-8.
[43] S. Juhela, H. Hyoty, M. Roivainen, T. Harkonen, A. Putto-Laurila, O. Simell and J. Ilonen,T-cell responses to enterovirus antigens in children with type1diabetes, Diabetes,49(2000),pp.1308-1313.
[2] Melnick JL, Shaw EW, Curnen EC. A Virus Isolated from Patients Diagnosed asNon-Paralytic Poliomyelitis or Aseptic Meningitis. Exp Biol Med1949July1,1949;71(3):344-349.
[3]闻玉梅主编.现代医学微生物学（第一版）1999:1205-1244.
[4] Fujimoto T, Iizuka S, Enomoto M, Abe K, Yamashita K, Hanaoka N, et al. Hand, foot, andmouth disease caused by coxsackievirus A6, Japan, Emerg Infect Dis2011Feb;18(2):337-339.
[5] Han JF, Jiang T, Fan XL, Yang LM, Yu M, Cao RY, et al. Recombination of humancoxsackievirus B5in hand, foot, and mouth disease patients, China. Emerg Infect Dis2012Feb;18(2):351-353.
[6] Yun S-H, Lee WG, Kim Y-C, Ju E-S, Lim B-K, Choi J-O, et al. Antiviral Activity ofCoxsackievirus B33C Protease Inhibitor in Experimental Murine Myocarditis. The Journalof Infectious Disease2012February1;205(3):491-497.
[7] Freeman R, McMahon MJ. Acute pancreatitis and serological evidence of infection withMycoplasma pneumoniae. Gut1978May;19(5):367-370.
[8] Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattre P, et al. Persistent infectionof human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesisin beta cells. J Virol2000Nov;74(21):10153-10164.
[9] Wong AH, Lau CS, Cheng PK, Ng AY, Lim WW. Coxsackievirus B3-associated asepticmeningitis: an emerging infection in Hong Kong. J Med Virol2011Mar;83(3):483-489.
[10] Huber S, Ramsingh AI. Coxsackievirus-induced pancreatitis. Viral Immunol2004;17(3):358-369.
[11] Gottenberg JE, Pallier C, Ittah M, Lavie F, Miceli-Richard C, Sellam J, et al. Failure toconfirm coxsackievirus infection in primary Sjogren's syndrome. Arthritis Rheum2006Jun;54(6):2026-2028.
[12] Rickels MR, Schutta MH, Markmann JF, Barker CF, Naji A, Teff KL.{beta}-Cell FunctionFollowing Human Islet Transplantation for Type1Diabetes. Diabetes2005January1,2005;54(1):100-106.
[13] Jaidane H, Hober D. Role of coxsackievirus B4in the pathogenesis of type1diabetes.Diabetes Metab2008Dec;34(6Pt1):537-548.
[14] Jaidane H, Sane F, Gharbi J, Aouni M, Romond MB, Hober D. Coxsackievirus B4and type1diabetes pathogenesis: contribution of animal models. Diabetes Metab Res Rev2009Oct;25(7):591-603.
[15] Lindberg AM, Stalhandske PO, Pettersson U. Genome of coxsackievirus B3. Virology1987Jan;156(1):50-63.
[16] Beck MA, Shi Q, Morris VC, Levander OA. Rapid genomic evolution of a non-virulentcoxsackievirus B3in selenium-deficient mice results in selection of identical virulent isolates.Nat Med1995May;1(5):433-436.
[17] Stadnick E, Dan M, Sadeghi A, Chantler JK. Attenuating mutations in coxsackievirus B3map to a conformational epitope that comprises the puff region of VP2and the knob of VP3.J Virol2004Dec;78(24):13987-14002.
[18] Smith CP, Clements GB, Riding MH, Collins P, Bottazzo GF, Taylor KW. Simultaneousonset of type1diabetes mellitus in identical infant twins with enterovirus infection. DiabetMed1998Jun;15(6):515-517.
[19] Muckelbauer JK, Kremer M, Minor I, Tong L, Zlotnick A, Johnson JE, et al. Structuredetermination of coxsackievirus B3to3.5A resolution. Acta Crystallogr D Biol Crystallogr1995Nov1;51(Pt6):871-887.
[20] Wunder T, Schumacher U, Friedrich RE. Coxsackie adenovirus receptor expression incarcinomas of the head and neck. Anticancer Res2012Mar;32(3):1057-1062.
[21] Kasman L, Onicescu G, Voelkel-Johnson C. Histone deacetylase inhibitors restore cellsurface expression of the coxsackie adenovirus receptor and enhance CMV promoter activityin castration-resistant prostate cancer cells. Prostate Cancer;2012:137-163.
[22] Tatrai E, Bedi K, Kovalszky I, Hartyanszky I, Laszik A, Acsady G, et al. No mutation buthigh mRNA expression of Coxsackie-Adenovirus Receptor was observed in both dilated andischemic cardiomyopathy. Forensic Sci Int2011Oct10;212(1-3):47-50.
[23] Kunin CM. Cellular Susceptibility to Enteroviruses. Bacteriol Rev1964Dec;28:382-390.
[24] Knowlton KU, Jeon ES, Berkley N, Wessely R, Huber S. A mutation in the puff region ofVP2attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant ofcoxsackievirus B3. J Virol1996Nov;70(11):7811-7818.
[25] van Kuppeveld FJ, van den Hurk PJ, Zoll J, Galama JM, Melchers WJ. Mutagenesis of thecoxsackie B3virus2B/2C cleavage site: determinants of processing efficiency and effects onviral replication. J Virol1996Nov;70(11):7632-7640.
[26] Moncorge O, Mura M, Barclay WS. Evidence for avian and human host cell factors thataffect the activity of influenza virus polymerase. J Virol2010Oct;84(19):9978-9986.
[27] Kinchington PR, Goins WF. Varicella zoster virus-induced pain and post-herpetic neuralgiain the human host and in rodent animal models. J Neurovirol2011Dec;17(6):590-599.
[28] Muckelbauer JK, Kremer M, Minor I, Diana G, Dutko FJ, Groarke J, et al. The structure ofcoxsackievirus B3at3.5A resolution. Structure1995Jul15;3(7):653-667.
[29] Liu GX, Lan JM, Chuai X, Gao ZY, Jin YH, Zhang YH, et al. Immune effects of fourcoxsackievirus B3VP1DNA fusion vaccines in mice. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi2010Feb;26(2):103-106.
[30] Yan LJ, Gao ZY, Li J, Lan JM, Jin YH, Xie LX, et al. Study on combined immunization ofrAd/MDC-VP1and pcDNA3/MDC-VP1against Coxsackievirus B3challenge in mice. XiBao Yu Fen Zi Mian Yi Xue Za Zhi2012Mar;28(3):228-231.
[31] Bayliss J, Harrison E, McLean CA. Progressive multifocal leukoencephalopathydevelopment is associated with mutations in JC virus capsid protein VP1that change thereceptor specificity of the virus. J Infect Dis2011Nov15;204(10):1643-1644.
[32] Zhong Z, Shi S, Han J, Zhang Z, Sun X. Anionic liposomes increase the efficiency ofadenovirus-mediated gene transfer to coxsackie-adenovirus receptor deficient cells. MolPharm2009Feb1;7(1):105-115.
[33] Yuen S, Smith J, Caruso L, Balan M, Opavsky MA. The coxsackie-adenovirus receptorinduces an inflammatory cardiomyopathy independent of viral infection. J Mol Cell Cardiol2011May;50(5):826-840.
[34] Shi Y, Fukuoka M, Li G, Liu Y, Chen M, Konviser M, et al. Regulatory T cells protect miceagainst coxsackievirus-induced myocarditis through the transforming growth factorbeta-coxsackie-adenovirus receptor pathway. Circulation2010Jun22;121(24):2624-2634.
[35] Dietel M, Hafner N, Jansen L, Durst M, Runnebaum IB. Novel splice variant CAR4/6of thecoxsackie adenovirus receptor is differentially expressed in cervical carcinogenesis. J MolMed (Berl)2011Jun;89(6):621-630.
[36] Caruso L, Yuen S, Smith J, Husain M, Opavsky MA. Cardiomyocyte-targeted overexpres-sion of the coxsackie-adenovirus receptor causes a cardiomyopathy in association withbeta-catenin signaling. J Mol Cell Cardiol2010Jun;48(6):1194-1205.
[37] Wen C, Gao ZY, Lan JM, Yan LJ, Chuai X, Li J, et al. The effects of inoculation route andadjuvant type on the immunizing potency of CVB3VP1protein. Xi Bao Yu Fen Zi Mian YiXue Za Zhi2011Oct;27(10):1086-1089.
[38] Nikolova I, Galabov AS, Petkova R, Chakarov S, Atanasov B. Disoxaril mutants of Coxsack-ievirus B1: phenotypic characteristics and analysis of the target VP1gene. Z Naturforsch C2011Nov-Dec;66(11-12):627-636.
[39] Wu X, Zhao T, Tian Y.[A bivalent VP1gene vaccine against Coxsackie virus B1/B3].Zhonghua Yi Xue Za Zhi2001Apr25;81(8):480-484.
[40] Nozawa K, Fritzler MJ, Ikeda K, Takasaki Y, Satoh M, Chan EK. Differential anti-Golgicomplex autoantibody production following murine lactate dehydrogenase-elevating virusinfection. Immunopharmacol Immunotoxicol2008;30(1):13-25.
[41] Desai P, Sexton GL, Huang E, Person S. Localization of herpes simplex virus type1UL37inthe Golgi complex requires UL36but not capsid structures. J Virol2008Nov;82(22):11354-11361.
[42] Hambleton S, Gershon M, Gershon A. The role of the trans-Golgi network in varicella zostervirus biology. Cell Mol Life Sci2004December1,2004;61(24):3047-3056.
[43] Lontok E, Corse E, Machamer CE. Intracellular Targeting Signals Contribute to Localizationof Coronavirus Spike Proteins near the Virus Assembly Site. J Virol2004June1,2004;78(11):5913-5922.
[44] Bertolotti-Ciarlet A, Smith J, Strecker K, Paragas J, Altamura LA, McFalls JM, et al. CellularLocalization and Antigenic Characterization of Crimean-Congo Hemorrhagic Fever VirusGlycoproteins. J Virol2005May15,2005;79(10):6152-6161.
[45] Jarvis MA, Jones TR, Drummond DD, Smith PP, Britt WJ, Nelson JA, et al. Phosphorylationof Human Cytomegalovirus Glycoprotein B (gB) at the Acidic Cluster Casein Kinase2Site(Ser900) Is Required for Localization of gB to the trans-Golgi Network and Efficient VirusReplication. J Virol2004January1,2004;78(1):285-293.
[46] Karabekian Z, Hanson LK, Slater JS, Krishna NK, Bolin LL, Kerry JA, et al. ComplexFormation among Murine Cytomegalovirus US22Proteins Encoded by Genes M139, M140,and M141. J Virol2005March15,2005;79(6):3525-3535.
[47] Hasan M, Krmpotic A, Ruzsics Z, Bubic I, Lenac T, Halenius A, et al. SelectiveDown-Regulation of the NKG2D Ligand H60by Mouse Cytomegalovirus m155Glycoprotein. J Virol2005March1,2005;79(5):2920-2930.
[48]刘发娣. CVB3对Hela细胞高尔基体及其细胞周期的影响;2009.
[49] Puthenveedu MA, Bachert C, Puri S, Lanni F, Linstedt AD. GM130and GRASP65-dependent lateral cisternal fusion allows uniform Golgi-enzyme distribution. Nat Cell Biol2006Mar;8(3):238-248.
[50] Feinstein TN, Linstedt AD. GRASP55regulates Golgi ribbon formation. Mol Biol Cell2008Jul;19(7):2696-2707.
[51] Nascimento R, Costa H, Parkhouse RM. Virus manipulation of cell cycle. Protoplasma2011Oct11.
[52] Kannan RP, Hensley LL, Evers LE, Lemon SM, McGivern DR. Hepatitis C virus infectioncauses cell cycle arrest at the level of initiation of mitosis. J Virol2011Aug;85(16):7989-8001.
[53] Maalouf K, Baydoun E, Rizk S. Kefir induces cell-cycle arrest and apoptosis inHTLV-1-negative malignant T-lymphocytes. Cancer Manag Res;2011March;3:39-47.
[54] Zhang SM, Song M, Yang TY, Fan R, Liu XD, Zhou PK. HIV-1Tat impairs cell cyclecontrol by targeting the Tip60, Plk1and cyclin B1ternary complex. Cell Cycle2012Mar15;11(6).
[55] Luo H, Zhang J, Dastvan F, Yanagawa B, Reidy MA, Zhang HM, et al. Ubiquitin-dependentproteolysis of cyclin D1is associated with coxsackievirus-induced cell growth arrest. J Virol2003Jan;77(1):1-9.
[56] Feuer R, Mena I, Pagarigan R, Slifka MK, Whitton JL. Cell cycle status affectscoxsackievirus replication, persistence, and reactivation in vitro. J Virol2002May;76(9):4430-4440.
[57] Feuer R, Mena I, Pagarigan RR, Hassett DE, Whitton JL. Coxsackievirus replication and thecell cycle: a potential regulatory mechanism for viral persistence/latency. Med MicrobiolImmunol2004May;193(2-3):83-90.
[58]黄孝天.柯萨奇B3病毒VP1与人细胞蛋白直接作用的研究.上海交通大学2005.
[59] Barr FA, Nakamura N, Warren G. Mapping the interaction between GRASP65and GM130,components of a protein complex involved in the stacking of Golgi cisternae. EMBO J1998Jun15;17(12):3258-3268.
[60] Mistchenko AS, Viegas M, Latta MP, Barrero PR. Molecular and epidemiologic analysis ofenterovirus B neurological infection in Argentine children. J Clin Virol2006Dec;37(4):293-299.
[61] Haarmann CM, Schwimmbeck PL, Mertens T, Schultheiss HP, Strauer BE. Identification ofserotype-specific and nonserotype-specific B-cell epitopes of coxsackie B virus usingsynthetic peptides. Virology1994May1;200(2):381-389.
[62] Boshart M, Weber F, Jahn G, Dorsch-Hasler K, Fleckenstein B, Schaffner W. A very strongenhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell1985Jun;41(2):521-530.
[63] Persic L, Roberts A, Wilton J, Cattaneo A, Bradbury A, Hoogenboom HR. An integratedvector system for the eukaryotic expression of antibodies or their fragments after selectionfrom phage display libraries. Gene1997Mar10;187(1):9-18.
[64] Romano M, Roupie V, Hamard M, Huygen K. Evaluation of the immunogenicity ofpBudCE4.1plasmids encoding mycolyl-transferase Ag85A and phosphate transport receptorPstS-3from Mycobacterium tuberculosis. Vaccine2006May22;24(21):4640-4643.
[65] Hou WR, Xie SN, Lu JL, Xi W, Luo X, Xiang M. Recombination of RegIII-proinsulin-pBudCE4.1plasmid and its therapeutic effect on STZ-induced type1diabetes mellitus. YaoXue Xue Bao2011Aug;45(8):987-994.
[66] Moeini H, Omar AR, Rahim RA, Yusoff K. Improving the potency of DNA vaccine againstchicken anemia virus (CAV) by fusing VP1protein of CAV to Marek's Disease Virus (MDV)type-1VP22protein. Virol J;2011March;8:119.
[67] Zhang HM, Ye X, Su Y, Yuan J, Liu Z, Stein DA, et al. Coxsackievirus B3infection activatesthe unfolded protein response and induces apoptosis through downregulation of p58IPK andactivation of CHOP and SREBP1. J Virol Sep;84(17):8446-8459.
[68] Esfandiarei M, McManus BM. Molecular biology and pathogenesis of viral myocarditis.Annu Rev Pathol2008;3:127-155.
[69] Bisel B, Wang Y, Wei JH, Xiang Y, Tang D, Miron-Mendoza M, et al. ERK regulates Golgiand centrosome orientation towards the leading edge through GRASP65. J Cell Biol2008Sep8;182(5):837-843.
[70] Tang D, Yuan H, Wang Y. The role of GRASP65in Golgi cisternal stacking and cell cycleprogression. Traffic2010Jun;11(6):827-842.
[71] Xiang Y, Wang Y. GRASP55and GRASP65play complementary and essential roles in Golgicisternal stacking. J Cell Biol2010Jan25;188(2):237-251.
[72]徐秋芳.宿主蛋白GM130在CVB3病毒性胰腺炎中的分子作用机制研究.2010.
[73] Wessels E, Duijsings D, Lanke KH, Melchers WJ, Jackson CL, van Kuppeveld FJ.Molecular determinants of the interaction between coxsackievirus protein3A and guaninenucleotide exchange factor GBF1. J Virol2007May;81(10):5238-5245.
[74] de Jong AS, Visch HJ, de Mattia F, van Dommelen MM, Swarts HG, Luyten T, et al. Thecoxsackievirus2B protein increases efflux of ions from the endoplasmic reticulum and Golgi,thereby inhibiting protein trafficking through the Golgi. J Biol Chem2006May19;281(20):14144-14150.
[75] Yao HL, Xiao ZH, Ren HY, Han JS, Liu ZW.[Study on inhibition of coxsackievirus B3infection in HeLa cell by short interfering RNA targeting2B protein]. Bing Du Xue Bao2007Jul;23(4):276-281.
[76] Marra P, Salvatore L, Mironov A, Jr., Di Campli A, Di Tullio G, Trucco A, et al. Thebiogenesis of the Golgi ribbon: the roles of membrane input from the ER and of GM130.Mol Biol Cell2007May;18(5):1595-1608.
[77] Feuer R, Whitton JL. Preferential coxsackievirus replication in proliferating/activated cells:implications for virus tropism, persistence, and pathogenesis. Curr Top Microbiol Immunol2008;323:149-173.
[78] Hobbs WE,2nd, DeLuca NA. Perturbation of cell cycle progression and cellular geneexpression as a function of herpes simplex virus ICP0. J Virol1999Oct;73(10):8245-8255.
[79] Lu M, Shenk T. Human cytomegalovirus UL69protein induces cells to accumulate in G1phase of the cell cycle. J Virol1999Jan;73(1):676-683.
[80] Barnitz RA, Chaigne-Delalande B, Bolton DL, Lenardo MJ. Exposed hydrophobic residuesin human immunodeficiency virus type1Vpr helix-1are important for cell cycle arrest andcell death. PLoS One2011Sep;6(9): e24924.
[81] Li L, Gu B, Zhou F, Chi J, Wang F, Peng G, et al. Human herpesvirus6suppresses T cellproliferation through induction of cell cycle arrest in infected cells in the G2/M phase. J Virol2011Jul;85(13):6774-6783.
[82] Gatza ML, Chandhasin C, Ducu RI, Marriott SJ. Impact of transforming viruses on cellularmutagenesis, genome stability, and cellular transformation. Environ Mol Mutagen2005Mar-Apr;45(2-3):304-325.
[83] Baydoun HH, Pancewicz J, Bai X, Nicot C. HTLV-I p30inhibits multiple S phase entrycheckpoints, decreases cyclin E-CDK2interactions and delays cell cycle progression. MolCancer2010;9:302.
[84] Ohkawa K, Ishida H, Nakanishi F, Hosui A, Ueda K, Takehara T, et al. Hepatitis C virus corefunctions as a suppressor of cyclin-dependent kinase-activating kinase and impairs cell cycleprogression. J Biol Chem2004Mar19;279(12):11719-11726.
[85]王灵枢,刘晶星,朱莉.柯萨奇B3病毒结构和非结构蛋白DNA疫苗诱导小鼠产生免疫应答的研究.中华微生物学和免疫学杂志2001;21(1):46-49.
[86] Ding FX, Wang F, Lu YM, Li K, Wang KH, He XW, et al. Multiepitope peptide-loadedvirus-like particles as a vaccine against hepatitis B virus-related hepatocellular carcinoma.Hepatology2009May;49(5):1492-1502.
[87] Goon P, Sonnex C, Jani P, Stanley M, Sudhoff H. Recurrent respiratory papillomatosis: anoverview of current thinking and treatment. Eur Arch Otorhinolaryngol2008Feb;265(2):147-151.
[88] Zhang L, Parham NJ, Zhang F, Aasa-Chapman M, Gould EA, Zhang H. Vaccination withcoxsackievirus B3virus-like particles elicits humoral immune response and protects miceagainst myocarditis. Vaccine2012Mar16;30(13):2301-2308.
[89] Chung YC, Ho MS, Wu JC, Chen WJ, Huang JH, Chou ST, et al. Immunization withvirus-like particles of enterovirus71elicits potent immune responses and protects miceagainst lethal challenge. Vaccine2008Mar28;26(15):1855-1862.
[90] Kui X, Sun M, Xie T, Wang W, Jiang L, Yan M, et al. The expression, purification, andimmunogenicity of a new chimeric virus-like particle. Viral Immunol2009Feb;22(1):49-56.
[91] Urakawa T, Ferguson M, Minor PD, Cooper J, Sullivan M, Almond JW, et al. Synthesis ofimmunogenic, but non-infectious, poliovirus particles in insect cells by a baculovirusexpression vector. J Gen Virol1989Jun;70(Pt6):1453-1463.
[92] Hiscox JA. RNA viruses: hijacking the dynamic nucleolus. Nat Rev Microbiol2007Feb;5(2):119-127.
[93] Zhou G, Doci CL, Lingen MW. Identification and functional analysis of NOL7nuclear andnucleolar localization signals. BMC Cell Biol2010;11(74):1471-2121
[94] Vihinen-Ranta M, Wang D, Weichert WS, Parrish CR. The VP1N-terminal sequence ofcanine parvovirus affects nuclear transport of capsids and efficient cell infection. J Virol2002Feb;76(4):1884-1891.
[95] Lombardo E, Ramirez JC, Garcia J, Almendral JM. Complementary roles of multiple nucleartargeting signals in the capsid proteins of the parvovirus minute virus of mice duringassembly and onset of infection. J Virol2002Jul;76(14):7049-7059.
[96] Lombardo E, Ramirez JC, Agbandje-McKenna M, Almendral JM. A beta-stranded motifdrives capsid protein oligomers of the parvovirus minute virus of mice into the nucleus forviral assembly. J Virol2000Apr;74(8):3804-3814.
[1] O. Jenkins, J. D. Booth, P. D. Minor and J. W. Almond, The Complete Nucleotide Sequenceof Coxsackievirus B4and Its Comparison to Other Members of the Picornaviridae, J. Gen.Virol.,68(1987), pp.1835-1848.
[2] D. D. Banker and J. L. Melnick, Isolation of Coxsackie virus (C virus) from North AlaskanEskimos, Am J Hyg,54(1951), pp.383-90.
[3] I. Zajac and R. L. Crowell, Effect of Enzymes on the Interaction of Enteroviruses withLiving Hela Cells, J Bacteriol,89(1965), pp.574-82.
[4] M. R. Rickels, M. H. Schutta, J. F. Markmann, C. F. Barker, A. Naji and K. L. Teff,{beta}-Cell Function Following Human Islet Transplantation for Type1Diabetes, Diabetes,54(2005), pp.100-106.
[5] C. Cordon-Cardo and C. Prives, At the Crossroads of Inflammation and Tumorigenesis, J.Exp. Med.,190(1999), pp.1367-1370.
[6] K. Klingel, S. Stephan, M. Sauter, R. Zell, B. M. McManus, B. Bultmann and R. Kandolf,Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets,J Virol,70(1996), pp.8888-95.
[7] R. Crowell and B. Landau, A short history and introductory background on thecoxsackieviruses of group B, Curr Top Microbiol Immunol,223(1997), pp.1-11.
[8] R. Freeman and M. J. McMahon, Acute pancreatitis and serological evidence of infectionwith Mycoplasma pneumoniae, Gut,19(1978), pp.367-70.
[9] T. Szopa, P. Titchener, N. Portwood and K. Taylor, Diabetes mellitus due to viruses--somerecent developments, Diabetologia,36(1993), pp.687-95.
[10] S. Tracy, K. M. Drescher, N. M. Chapman, K. S. Kim, S. D. Carson, S. Pirruccello, P. H.Lane, J. R. Romero and J. S. Leser, Toward testing the hypothesis that group Bcoxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabeticmice with CVB markedly lowers diabetes incidence, J Virol,76(2002), pp.12097-111.
[11] H. Champsaur, G. Bottazzo, J. Bertrams, R. Assan and C. Bach, Virologic, immunologic, andgenetic factors in insulin-dependent diabetes mellitus, J Pediatr,100(1982), pp.15-20.
[12] J. Yoon, M. Austin, T. Onodera and A. Notkins, Isolation of a virus from the pancreas of achild with diabetic ketoacidosis, N. Engl. J. Med.,300(1979), pp.1173-1179.
[13] Reviews and Notes: Gastroenterology: Acute Pancreatitis: Diagnosis and Therapy, AnnIntern Med,120(1994), pp.352-d-.
[14] P. Lankisch, S. Burchard-Reckert, M. Petersen, D. Lehnick, C. Schirren, H. Kohler, F.Stockmann, H. Peiper and W. Creutzfeldt, Morbidity and mortality in602patients with acutepancreatitis seen between the years1980-1994, Z Gastroenterol,34(1996), pp.371-7.
[15] B. Arnesjo, T. Eden, I. Ihse, E. Nordenfelt and B. Ursing, Enterovirus infections in acutepancreatitis-a possible etiological connection, Scand J Gastroenterol,11(1976), pp.645-9.
[16] P. Capner, R. Lendrum, D. J. Jeffries and G. Walker, Viral antibody studies in pancreaticdisease, Gut,16(1975), pp.866-70.
[17] Z. Ozsvar, J. Deak and A. Pap, Possible role of Coxsackie-B virus infection in pancreatitis,Int J Pancreatol,11(1992), pp.105-8.
[18] D. A. Bass, Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophildynamics during acute inflammation, J Clin Invest,56(1975), pp.870-9.
[19] A. I. Ramsingh, Coxsackieviruses and pancreatitis, Front Biosci,2(1997), pp. e53-62.
[20] A. I. Ramsingh, W. T. Lee, D. N. Collins and L. E. Armstrong, Differential recruitment of Band T cells in coxsackievirus B4-induced pancreatitis is influenced by a capsid protein, JVirol,71(1997), pp.8690-7.
[21] S. E. Ostrowski, A. A. Reilly, D. N. Collins and A. I. Ramsingh, Progression or resolution ofcoxsackievirus B4-induced pancreatitis: a genomic analysis, J Virol,78(2004), pp.8229-37.
[22] V. Ramiya, M. Maraist, K. Arfors, D. Schatz, A. Peck and J. Cornelius, Reversal ofinsulin-dependent diabetes using islets generated in vitro from pancreatic stem cells, NatMed,6(2000), pp.278-82.
[23] H. Elsasser, G. Adler and H. Kern, Time course and cellular source of pancreatic regenerationfollowing acute pancreatitis in the rat, Pancreas,1(1986), pp.421-9.
[24] S. Bonner-Weir, L. Baxter, G. Schuppin and F. Smith, A second pathway for regeneration ofadult exocrine and endocrine pancreas. A possible recapitulation of embryonic development,Diabetes,42(1993), pp.1715-1720.
[25] M. Caggana, P. Chan and A. Ramsingh, Identification of a single amino acid residue in thecapsid protein VP1of coxsackievirus B4that determines the virulent phenotype, J. Virol.,67(1993), pp.4797-4803.
[26] D. M. Potvin, D. W. Metzger, W. T. Lee, D. N. Collins and A. I. Ramsingh, Exogenousinterleukin-12protects against lethal infection with coxsackievirus B4, J Virol,77(2003), pp.8272-9.
[27] A. Ramsingh, J. Slack, J. Silkworth and A. Hixson, Severity of disease induced by apancreatropic Coxsackie B4virus correlates with the H-2Kq locus of the majorhistocompatibility complex, Virus Res,14(1989), pp.347-58.
[28] S. Tracy, K. Hofling, S. Pirruccello, P. H. Lane, S. M. Reyna and C. J. Gauntt, Group Bcoxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypesin mice, J Med Virol,62(2000), pp.70-81.
[29] D. Serreze, E. Ottendorfer, T. Ellis, C. Gauntt and M. Atkinson, Acceleration of type1diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactiveT-cells in pancreatic islets, Diabetes,49(2000), pp.708-711.
[30] R. Blay, K. Simpson, K. Leslie and S. Huber, Coxsackievirus-induced disease. CD4+cellsinitiate both myocarditis and pancreatitis in DBA/2mice, Am J Pathol,135(1989), pp.899-907.
[31] A. Henke, H. Launhardt, K. Klement, A. Stelzner, R. Zell and T. Munder, Apoptosis inCoxsackievirus B3-Caused Diseases: Interaction between the Capsid Protein VP2and theProapoptotic Protein Siva, J. Virol.,74(2000), pp.4284-4290.
[32] B. Jacobs and J. Langland, When two strands are better than one: the mediators andmodulators of the cellular responses to double-stranded RNA, Virology,219(1996), pp.339-49.
[33] K. L. Peters, H. L. Smith, G. R. Stark and G. C. Sen, IRF-3-dependent, NFkappa B-andJNK-independent activation of the561and IFN-beta genes in response to double-strandedRNA, PNAS,99(2002), pp.6322-6327.
[34] J. C. Castelli, B. A. Hassel, K. A. Wood, X.-L. Li, K. Amemiya, M. C. Dalakas, P. F.Torrence and R. J. Youle, A Study of the Interferon Antiviral Mechanism: ApoptosisActivation by the2-5A System, J. Exp. Med.,186(1997), pp.967-972.
[35] K. V. S. Prasad, Z. Ao, Y. Yoon, M. X. Wu, M. Rizk, S. Jacquot and S. F. Schlossman, CD27,a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, aproapoptotic protein, PNAS,94(1997), pp.6346-6351.
[36] G. Geiss, G. Jin, J. Guo, R. Bumgarner, M. G. Katze and G. C. Sen, A Comprehensive Viewof Regulation of Gene Expression by Double-stranded RNA-mediated Cell Signaling, J. Biol.Chem.,276(2001), pp.30178-30182.
[37] A. Kumar, J. Haque, J. Lacoste, J. Hiscott and B. Williams, Double-Stranded RNA-Dependent Protein Kinase Activates Transcription Factor NF-{kappa}B by PhosphorylatingI{kappa}B, PNAS,91(1994), pp.6288-6292.
[38] C. Lowenstein, S. Hill, A. Lafond-Walker, J. Wu, G. Allen, M. Landavere, N. Rose and A.Herskowitz, Nitric oxide inhibits viral replication in murine myocarditis, J Clin Invest,97(1996), pp.1837-43.
[39] W. Fiers, R. Beyaert, E. Boone, S. Cornelis, W. Declercq, E. Decoster, G. Denecker, B.Depuydt, D. De Valck, G. De Wilde, V. Goossens, J. Grooten, G. Haegeman, K. Heyninck, L.Penning, S. Plaisance, K. Vancompernolle, W. Van Criekinge, P. Vandenabeele, W. VandenBerghe, M. Van de Craen, V. Vandevoorde and D. Vercammen, TNF-induced intracellularsignaling leading to gene induction or to cytotoxicity by necrosis or by apoptosis, J Inflamm,47(1995), pp.67-75.
[40] G. L. Freeman, J. T. Colston, M. Zabalgoitia and B. Chandrasekar, Contractile depression andexpression of proinflammatory cytokines and iNOS in viral myocarditis, Am J Physiol HeartCirc Physiol,274(1998), pp. H249-258.
[41] C. Badorff, G. Lee, B. Lamphear, M. Martone, K. Campbell, R. Rhoads and K. Knowlton,Enteroviral protease2A cleaves dystrophin: evidence of cytoskeletal disruption in anacquired cardiomyopathy, Nat Med,5(1999), pp.320-6.
[42] A. Theofilopoulos, The basis of autoimmunity: Part I. Mechanisms of aberrantself-recognition, Immunol Today,16(1995), pp.90-8.
[43] S. Juhela, H. Hyoty, M. Roivainen, T. Harkonen, A. Putto-Laurila, O. Simell and J. Ilonen,T-cell responses to enterovirus antigens in children with type1diabetes, Diabetes,49(2000),pp.1308-1313.