MDV CVI988弱毒疫苗株VP22蛋白转导功能研究
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摘要
血清I型马立克氏病病毒(Marek’s disease virus serotype 1,MDV-1)的UL49h基因与I型单纯疱疹病毒(HSV-1)UL49同源,编码病毒被膜蛋白VP22,分子量约27.6kD,是病毒被膜的主要成分。现已证实,MDV-1 VP22对病毒的复制和传播有着非常重要的作用。Dorange等发现MDV-1 VP22具有与HSV-1相似的蛋白转导功能。Hung等研究发现MDV-1 VP22能增强人16型乳头状瘤病毒(HPV-16)E7抗原融合表达的免疫效果,主要产生CD8+ T细胞介导的细胞免疫应答。
     本研究利用无致病性的CVI988/Rispens疫苗株扩增VP22基因,结果发现其C端缺失6个氨基酸,即201TKSERT206,对CVI988 VP22蛋白转导功能的研究结果提示:CVI988 VP22可作为一种高效便捷的蛋白转运工具,对于弥补DNA免疫缺陷和提高治疗性物质的转导效率具有非常重要的意义。
     1不同致病型马立克氏病病毒VP22蛋白的序列比较和分析
     用MDV-1 CVI988/Rispens株、GA株、RB1B株和648A株,MDV-2 Z4株和FC126株分别感染鸭胚成纤维细胞或鸡胚成纤维细胞,待出现大量空斑时,提取总DNA。根据已发表的MDV GA株VP22序列设计引物,成功扩增出MDV-1不同毒株的VP22基因。将PCR产物克隆T载体并测序分析,结果发现:强毒株GA株、超强毒RB1B株和特超强毒648A株的VP22长度保持750bp,但CVI988弱毒株的VP22基因C端缺失18bp,即存在一个6氨基酸残基的缺失性突变:201TKSERT206。
     2 CVI988弱毒疫苗株VP22羧基端原核表达及特异性抗体的制备
     设计特异性引物,扩增全长VP22、CVI988 VP22的羧基端区域(VP22C:aa94~243)、VP22末端区(VP22T:aa207~249)、缺失N端的VP22(VP22H:aa19~243)。将BamHⅠ、EcoRⅠ双酶切PCR产物,克隆入pGEX-6P-1载体中,转化BL21(DE3)细菌,经IPTG诱导表达,结果发现:VP22C获得了高效可溶性表达。SDS-PAGE分离阳性条带,采用切胶免疫或用诱导后的细菌经超声波裂解的
The UL49 homolog (UL49h) gene of Marek’s disease virus serotype 1 (MDV-1) encodes the viral protein 22 (VP22) of 27.6kD with a homology of about 25% to the VP22 of Herpes Simplex virus type 1 (HSV-1). In HSV-1, VP22 is a novel translocating protein with a potential protein tranduction domain (PTD) in its cytoplamic region, which has been successfully used to enhance the delivery and therapeutic or immuno-stimulatory effects of several proteins in vitro or in vivo. The VP22 protein in the virulent MDV-1 strain RB1B has an intercellular trafficking function similar to that of HSV-1, which appears to be indispensable for cell-to-cell spread and propagation of MDV-1. A DNA vaccine containing the E7 gene of human papillomavirus type 16 linked to MDV-1 VP22 gene has a significantly increased immunogenicity in terms of stimulating E7-Specific CD8+ T cells, suggesting that the MDV-1 VP22 is an alternative transduction protein for enhancing vaccine potency.
     Our previous data showed that the VP22 of the attenuated MDV-1 strain CVI988/Rispens had a deletion of 201TKSERT206 compared to that of the oncogenic GA strain and other virulent strains. To investigate the influence of the deletion on the intercellular trafficking of the VP22 protein, antibodies specific for the carboxyl terminus of CVI988 VP22 was prepared by immunizing mice with truncated protein expressed in E. coli, and used to detect the expression and functions of VP22 and its truncated proteins/peptides in different eukocytic systems. It was described that the preliminary applications of VP22 in avirulent vaccine strain CVI988/Rispens and in the strategies for novel vaccines.
     The sequence comparison of VP22 protein amplified from different pathotypes of Marek’s disease virus
     Several fragments of VP22 gene were amplified from total DNAs, which were extracted
引文
[1] Abdallah B, et al. A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyehtylenimine. Human Gene Ther. 1996, 7: 1947-1954.
    [2] Ace C I, et al. Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. J. Virol. 1989, 63: 2260-2269.
    [3] Ace C I, et al. Mutational analysis of the herpes simplex virus type I trans-inducing factor Vmw65. J. Gen. Virol. 1988, 69: 2595-2605.
    [4] Achille F, et al. Avian adenovirus CELO recombinants expressing VP2 of infectious bursal disease virus induce protection against bursal disease in chickens. Vaccine. 2004, 22: 2351–2360
    [5] Aints A, et al. Intercellular spread of GFP-VP22. J Gene Med. 1999, 1(4): 275-9.
    [6] Aints A, et al. Mapping of herpes simplex virus-1 VP22 functional domains for inter and subcellular protein targeting. Gene Ther. 2001, 8(14): 1051-6.
    [7] Anna K, et al. Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein. J. Virol. 2001, 75(18): 8697-8711.
    [8] Anna M, et al. Herpes simplex virus tegument protein VP22 contains overlapping domains for cytoplasmic localization, microtubule interaction, and chromatin binding. J.Virol, 2002, 76(10): 4961-4970.
    [9] Antoine M, et al. Identification of an unconventional nuclear localization signal in human ribosomal protein S2. Biochem Biophys Res Commun. 2005, 335(1): 146-53.
    [10] Attrill H L, et al. The herpes simplex virus type 1 US11 protein binds the coterminal UL12, UL13, and UL14 RNAs and regulates UL13 expression in vivo. J Virol. 2002, 76(16): 8090-100.
    [11] Azad A A, et al. Physicochemical and immunological characterization of recombinant host-protective antigen (VP2) of infectious bursal disease virus. Vaccine. 1991, 9(10): 715-22.
    [12] Barbara G K, et al. Pseudorabies virus UL36 tegument protein physically interacts with the UL37 protein. J. Virol. 2002, 76(6): 3065-3071.
    [13] Barbe-Tuana F M, et al. Modified location of the major histocompatibility protein Kb by co-delivery with VP22 protein. Biomol Eng. 2004, 21(1): 27-31.
    [14] Batterson W and Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of α genes. J. Virol. 1983, 46: 371-377.
    [15] Bennett RP, et al. Protein delivery using VP22. Nat Biotechnol. 2002, 20(1):20.
    [16] Bernard R and Amy ES. Herpes Simplex Viruses and their Replication. In: Fundamental Virology. (Third Edition). By: B.N Fields, D.M. Howley, et al. Lippincott-Raven Publishers, Philadelphia, 1996: 1043-1108.
    [17] Bian J, et al. Engineered cell therapy for sustained local myocardial delivery of nonsecreted proteins. Cell Transplant. 2006, 15(1): 67-74.
    [18] Blaho J A, et al. An amino acid sequence shared by the herpes simplex virus 1 alpha regulatory proteins 0, 4, 22, and 27 predicts the nucleotidylylation of the UL21, UL31, UL47, and UL49 gene products. J Biol Chem. 1994, 69(26): 17401-10.
    [19] Blouin A, et al. Assessment of the subcellular localization of the herpes simplex virus structural protein VP22 in the absence of other viral gene products. Virus Res. 2001, 81(1-2): 57-68.
    [20] Boenicke L, et al. Efficient dose-dependent and time-dependent protein transduction of pancreatic carcinoma cells in vitro and in vivo using purified VP22-EGFP fusion protein. J Mol Med. 2003, 81(3): 205-13.
    [21] Bogerd H P, et al. Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Mol Cell Biol. 1996, 16(8): 4207-14.
    [22] Bowzard J B, et al. Membrane targeting properties of a herpesvirus tegument protein-retrovirus Gag chimera. J Virol. 2000 Sep;74(18):8692-9.
    [23] Brack A R, et al. Inhibition of virion maturation by simultaneous deletion of glycoproteins E, I, and M ofpseudorabies virus. J. Virol. 1999, 73: 5364-5372.
    [24] Brewis N, et al. Evaluation of VP22 spread in tissue culture. J Virol. 2000, 74(2): 1051-6.
    [25] Brewis N, et al. Particle assembly incorporating a VP22-BH3 fusion protein, facilitating intracellular delivery, regulated release, and apoptosis. Mol Ther. 2003, 7(2): 262-70.
    [26] Brignati M J, et al. Membrane association of VP22, a herpes simplex virus type 1 tegument protein. J Virol. 2003, 77(8): 4888-98.
    [27] Campbell M E, et al. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J. Mol. Biol. 1984, 180: 1-19.
    [28] Cao Y C, et al. Vaccination against very virulent infectious bursal disease virus using recombinant T4 bacteriophage displaying viral protein VP2. Acta Biochim Biophys Sin (Shanghai). 2005, 37(10): 657-64.
    [29] Carpenter D E, Misra V. The most abundant protein in bovine herpes 1 virions is a homologue of herpes simplex virus type 1 UL47. J Gen Virol. 1991, 72(12): 3077-84.
    [30] Carpenter D E, Misra V. The most abundant protein in bovine herpes 1 virions is a homologue of herpes simplex virus type 1 UL47. J Gen Virol. 1991, 72(12): 3077-84.
    [31] Cashman S M, et al. Intercellular trafficking of adenovirus-delivered HSV VP22 from the retinal pigment epithelium to the photoreceptors-implications for gene therapy. Mol Ther. 2002, 6(6): 813-23.
    [32] Chang Y E, et al. The product of the UL31 gene of herpes simplex virus 1 is a nuclear phosphoprotein, which partitions with the nuclear matrix. J. Virol. 1993, 67: 6348-6356.
    [33] Chang Y E, et al. The null mutant of the UL31 gene of herpes simplex virus 1: construction and phenotype in infected cells. J. Virol. 1997, 71: 8307-8315.
    [34] Chatzidaki E E, et al. Use of HSV-1 VP22 protein as a tool for gene & protein therapy for. cystic fibrosis. Mol Ther 2002, 5: S232.
    [35] Chen L, et al. Properties of two EBV Mta nuclear export signal sequences. Virology. 2001, 288(1): 119-28.
    [36] Cheng G et al. Signals that dictate nuclear, nucleolar, and cytoplasmic shuttling of the gamma(1)34.5 protein of herpes simplex virus type 1. J Virol. 2002, 76(18): 9434-45.
    [37] Cheng W F, et al. Enhancement of Sindbis vrus self-replicating RNA vaccine potency by linkage of Herpes simplex virus type 1 VP22 protein to antigen. J. Virol. 2001, 75(5): 2368-2376.
    [38] Cheng W F, et al. Cancer immunotherapy using Sindbis virus replicon particles encoding a VP22-antigen fusion. Hum Gene Ther. 2002, 13(4): 553-68.
    [39] Chhabra A, et al. Cross-presentation of a human tumor antigen delivered to dendritic cells by HSV VP22-mediated protein translocation. Eur J Immunol. 2004, 34(10): 2824-33.
    [40] Chi J H, et al. The cytoplasmic tail of herpes simplex virus envelope glycoprotein D binds to the tegument protein VP22 and to capsids. J Gen Virol. 2005, 86(2): 253-61.
    [41] Chunfu Z, et al. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1. Virology. 2004, 324: 327– 339.
    [42] Coulter L, et al. A mutant of herpes simplex virus type 1 in which the UL13 protein kinase gene is disrupted. J. Gen. Virol. 1993, 74: 387-395.
    [43] Cousens D J, et al. The C-terminal 79 amino acids of the herpes simplex virus regulatory protein, Vmw65, effectively activate transcription in yeast and mammalian cells in chimeric DNA binding proteins. EMBO J. 1989, 8: 2337-2342.
    [44] Cuchet D, et al. Characterization of antiproliferative and cytotoxic properties of the HSV-1 immediate-early ICPo protein. J Gene Med. 2005, 7(9): 1187-99.
    [45] Cunningham C, et al. The UL13 virion protein of herpes simplex virus type 1 is phosphorylated by a novel virus-induced protein kinase. J. Gen. Virol. 1992, 73: 303-311.
    [46] Daikoku T, et al. Purification and Characterization of the Protein Kinase Encoded by the UL13 Gene of Herpes Simplex Virus Type 2. Vorology. 1997, 235: 82–93.
    [47] del Rio T, et al. The pseudorabies virus VP22 homologue (UL49) is dispensable for virus growth in vitro and has no effect on virulence and neuronal spread in rodents. J Virol. 2002, 76(2): 774-82.
    [48] del Rio T, et al. Actin is a component of the compensation mechanism in pseudorabies virus virions lacking the major tegument protein VP22. J Virol. 2005, 79(13): 8614-9.
    [49] Derer W, et al. Direct protein transfer to terminally differentiated muscle cells. J Mol Med. 1999, 77(8): 609-13.
    [50] Derer W, et al. A novel approach to induce cell cycle reentry in terminally differentiated muscle cells. FASEB J. 2002, 16(1): 132-3.
    [51] Desai P J. A null mutation in the UL36 gene of herpes simplex virus type 1 results in accumulation of unenveloped DNA-filled capsids in the cytoplasm of infected cells. J. Virol. 2000, 74(24): 11608-18.
    [52] Desai P, et al. A null mutation in the gene encoding the UL37 polypeptide of herpes simplex virus type 1 abrogates virus maturation. J. Virol. 2001, 75: 10259-10271.
    [53] Deshayes S, et al. Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci. 2005, 62(16): 1839-49.
    [54] Derossi D, et al. The third helix of the Antennapedia homeodomain ranslocates through biological membranes. J. Biol. Chem. 1994, 269: 10444–10450.
    [55] Derossi D, et al. Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol. 1998, 8: 84-87.
    [56] De Wind N, et al. Herpesviruses encode an unusual protein-serine/threonine kinase which is nonessential for growth in cultured cells. J. Virol. 1992, 66: 5200-5209.
    [57] Diane J H, et al. Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes. Vaccine. 2004, 22: 1249–1259.
    [58] Dilber M S, et al. Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22. Gene Ther. 1999, 6(1): 12-21.
    [59] Donnelly M, Elliott G. Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus infection. J Virol. 2001, 75(6): 2575-83.
    [60] Donnelly M, Elliott G. Nuclear localization and shuttling of herpes simplex virus tegument protein VP13/14. J Virol. 2001, 75(6): 2566-74.
    [61] Dorange F, et al. Characterization of Marek's disease virus serotype 1 (MDV-1) deletion mutants that lack UL46 to UL49 genes: MDV-1 UL49, encoding VP22, is indispensable for virus growth. J. Virol. 2002, 76: 1959-1970.
    [62] Dorange F, et al. Marek's disease virus (MDV) homologues of herpes simplex virus type 1 UL49 (VP22) and UL48 (VP16) genes: high-level expression and characterization of MDV-1 VP22 and VP16. J Gen Virol. 2000, 81(9): 2219-30.
    [63] El-Andaloussi S, et al. Cell-penetrating peptides: mechanisms and applications. Curr Pharm Des. 2005, 11(28): 3597-611.
    [64] Elliott G, et al. The herpes simplex virus type 1 tegument protein VP22 is encoded by gene UL49. J Gen Virol. 1992, 73 (3): 723-726.
    [65] Elliott G, et al. VP16 interacts via its activation domain with VP22, a tegument protein of Herpes simplex sirus, and is relocated to a novel macromolecular assembly in co-expressing cells. J. Virol. 1995, 69(12): 7932–7941.
    [66] Elliott G, et al. Phosphorylation of the herpes simplex virus type 1 tegument protein VP22. Virology. 1996, 226(1): 140-145.
    [67] Elliott G and Peter O'Hare. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell. 1997, 88(2): 223-233.
    [68] Elliott G, O'Hare P. Herpes simplex virus type 1 tegument protein VP22 induces the stabilization and hyperacetylation of microtubules. J Virol. 1998, 72(8): 6448-55.
    [69] Elliott G, et al. Identification of phosphorylation sites within the herpes simplex virus tegument protein VP22. J. Virol. 1999, 73(7): 6203-6206.
    [70] Elliott G, O'Hare P. Intercellular trafficking of VP22-GFP fusion proteins. Gene Ther. 1999, 6(1): 149-51.
    [71] Elliott G, O'Hare P. Live-cell analysis of a green fluorescent protein-tagged herpes simplex virus infection. J Virol. 1999, 73(5): 4110-9.
    [72] Elliott G, P O'Hare. Cytoplasm-to-nucleus translocation of a herpesvirus tegument protein during cell division. J. Virol. 2000, 74: 2131-2141.
    [73] Elliott G, et al. Deletion of the herpes simplex virus VP22-encoding gene (UL49) alters the expression, localization, and virion incorporation of ICP0. J Virol. 2005, 79(15): 9735-45.
    [74] Fahey K J, et al. Virus-neutralizing and passively protective monoclonal antibodies to infectious bursal disease virus of chickens. Avian Dis. 1991, 35(2): 365-73.
    [75] Falnes P O, et al. Ability of the Tat basic domain and VP22 to mediate cell binding, but not membrane translocation of the diphtheria toxin A-fragment. Biochemistry. 2001, 40(14): 4349-58.
    [76] Fang B, Xu B, Koch P, Roth JA. Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells. Gene Ther. 1998, 5(10): 1420-4.
    [77] Fawell S, et al. Tat-mediated delivery of heterologous proteins into cells. Proc. Natl. Acad. Sci. USA. 1994, 91: 664-668
    [78] Feltquate D M, et al. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 1997, 158: 2278-84.
    [79] Ford K G, et al. Protein transduction: an alternative to genetic intervention? Gene Ther. 2001, 8(1): 1-4.
    [80] Fodor I, et al. Induction of protective immunity in chickens immunized with plasmid DNA encoding infectious bursal disease virus antigens. Acta Vet Hung. 1999, 47(4): 481-92.
    [81] Frankel A D, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988, 55(6): 1189-93.
    [82] Fuchs W, et al. The interacting UL31 and UL34 gene products of pseudorabies virus are involved in egress from the host-cell nucleus and represent components of primary enveloped but not of mature virions. J. Virol. 2002, 71: 364-378.
    [83] Fuchs W, et al. Physical interaction between envelope glycoproteins E and M of pseudorabies virus and the major tegument protein UL49. J Virol. 2002, 76(16): 8208-17.
    [84] Futaki S. Oligoarginine vectors for intracellular delivery: Design and cellular-uptake mechanisms. Cell Transplant. 2005, 14: 637-45.
    [85] Futaki S. Arginine-rich peptides: potential for intracellular delivery of macromolecules and the mystery of the translocation mechanisms. Int. J. Pharm. 2002, 245: 1-7.
    [86] Geiss B J, et al. Herpes simplex virus 2 VP22 phosphorylation induced by cellular and viral kinases does not influence intracellular localization. Virology. 2004, 330(1): 74-81.
    [87] Gershon A A, et al. Intracellular transport of newly synthesized varicella-zoster virus: final envelopment in the trans-Golgi network. J. Virol. 1994, 68: 6372-6390.
    [88] Godbey W T, et al. Poly(ethylenimine) and its role in gene delivery. J Control Rel. 1999, 60: 149-160.
    [89] Gorlich D, Mattaj. I W. Nucleocytoplasmic transport. Science. 1996. 271: 1513-1518.
    [90] Goula D, et al. Rapid crossing of the pulmonary endoehtlial barrier by polyethylenimine/DNA complexes. Gene Ther. 2000, 7: 499.
    [91] Granzow H, et al. Ultrastructural analysis of the replication cycle of pseudorabies virus in cell culture: a reassessment. J. Virol. 1997, 71: 2072-2082.
    [92] Granzow H, et al. Egress of alpha herpesviruses: comparative ultrastructural study. J Virol. 2001, 75: 3675-84.
    [93] Greco O, et al. VP22-mediated intercellular transport for suicide gene therapy under oxic and hypoxic conditions. Gene Ther. 2005, (12): 974-9.
    [94] Green K L, et al. Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy. Hum Gene Ther. 2006, 17(2): 147-57.
    [95] Green M, Loewenstein PM. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell. 1988, 55(6): 1179-88.
    [96] Geiss B J, et al. Herpes simplex virus 2 VP22 phosphorylation induced by cellular and viral kinases does not influence intracellular localization. Virology. 2004, 330(1): 74-81.
    [97] Geiss B J, et al. Temporal regulation of herpes simplex virus type 2 VP22 expression and phosphorylation. J Virol. 2001, 75(22): 10721-9.
    [98] Gupta B, et al. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev. 2005, 57(4): 637-51.
    [99] Gupta B, Torchilin V P. Transactivating transcriptional activator-mediated drug delivery. Expert Opin Drug Deliv. 2006, 3(2): 177-90.
    [100] Hafezi W, et al. Herpes simplex virus tegument protein VP22 contains an internal VP16 interaction domain anda C-terminal domain that are both required for VP22 assembly into the virus particle. J Virol. 2005, 79(20): 13082-93.
    [101] Hagglund R, Roizman B. Role of ICP0 in the strategy of conquest of the host cell by herpes simplex virus 1. J Virol. 2004, 78(5): 2169-78.
    [102] Hagmann M, et al. The VP16 paradox: herpes simplex virus VP16 contains a long-range activation domain but within the natural multiprotein complex activates only from promoter-proximal positions. J Virol. 1997, 71(8): 5952-62.
    [103] Hakkarainen T, et al. VP22 does not significantly enhance enzyme prodrug cancer gene therapy as a part of a VP22-HSVTk-GFP triple fusion construct. J Gene Med. 2005, 7(7): 898-907.
    [104] Hammerschmid M, et al. Scanning mutagenesis of the arginine-rich region of the human immunodeficiency virus type 1 Rev trans activator. J. Virol. 1994, 68: 7329-7335.
    [105] Harms J S, et al. Distinctions between bovine herpesvirus 1 and herpes simplex virus type 1 VP22 tegument protein subcellular associations. J Virol. 2000, 74(7): 3301-3312.
    [106] Heine H G, et al. Modification of infectious bursal disease virus antigen VP2 for cell surface location fails to enhance immunogenicity. Virus Res. 1994, 32(3): 313-28.
    [107] Heine J W, et al. Proteins specified by herpes simplex virus. Ⅻ. The virion polypeptides of type 1 strains. J. Virol. 1974, 14: 640-651.
    [108] Henderson G, et al. The Bovine herpesvirus 1 gene encoding infected cell protein 0 (bICP0) can inhibit interferon-dependent transcription in the absence of other viral genes. J Gen Virol. 2005, 86(10): 2697-702.
    [109] Hermann M, et al. Research on IBDV- the past, the present and the future. Vet. Microbio. 2003, 97: 153-65.
    [110] Hicks G R, Raikhel N V. Protein import into the nucleus: an integrated view. Ann Rev Cell Develop Biol. 1995, 11: 155-188.
    [111] Honess R W and Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J. Virol. 1974, 14: 8-19.
    [112] Hua C C, et al. DNA-mediated vaccination against infectious bursal disease in chickens. Vaccine. 2002, 20: 328–335.
    [113] Hua C C, et al. DNA vaccination with plasmids containing various fragments of large segment genome of infectious bursal disease virus. Vaccine. 2003, 21: 507–513.
    [114] Hung C F, et al. Improving vaccine potency through intercellular spreading and enhanced MHC class I presentation of antigen. J Immunol. 2001, 166(9): 5733-40.
    [115] virus –specific antibodes. Vet. Immun. Immunopath. 2002, 89: 149-58.
    [116] Hung C F, et al. Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen. J Virol. 2002, 76(6): 2676-82.
    [117] Hung-Yueh Yeh, et al. Protective immunity against infectious bursal disease virus in chickens in the absence of virus-specific antibodies. Vet Immunol Immunopathol. 2002, 89(3-4): 149-58.
    [118] Izumiya Y, et al. Identification and transcriptional analysis of the homologues of the herpes simplex virus type 1 UL41 to UL51 genes in the genome of nononcogenic Marek's disease virus serotype 2. J Gen Virol. 1998, 79(8): 1997-2001.
    [119] Jamie C Y, et al. Nuclear Localizations of the Herpes Simplex Virus Type 1 Tegument Proteins VP13/14, vhs, and VP16 Precede VP22-Dependent Microtubule Reorganization and VP22 Nuclear Import. J. Virol. 2005, 79(8): 4730–4743.
    [120] Jans D A, et al. Nuclear targeting of the serine protease granzyme A (fragmentin-1). J Cell Sci. 1998, 111(17): 2645-54.
    [121] Jarver P, Langel U. The use of cell-penetrating peptides as a tool for gene regulation. Drug Discov Today. 2004, 9(9): 395-402.
    [122] Jehangir S W, Steven F D. Protein transduction technology. Analytical biotech. 2000, 52-56.
    [123] Jens A L, Lindsay J W. “translocatory proteins” and “protein transduction domains”: A critical analysis of their biological fffects and the underlying mechanisms. Molecular Therapy. 2003, 8(1): 13-20.
    [124] Kato A, et al. Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J Virol. 2006, 80(3): 1476-86.
    [125] Kelleher R J 3rd, et al. Yeast and human TFIIDs are interchangeable for the response to acidic transcriptional activators in vitro. Genes Dev. 1992, 6(2): 296-303.
    [126] Kim S J, et al. Protection against very virulent infectious bursal disease virus in chickens immunized with DNA vaccines. Vet Microbiol. 2004, 101(1): 39-51.
    [127] Kim T W, et al. Vaccination with a DNA vaccine encoding herpes simplex virus type 1 VP22 linked to antigen generates long-term antigen-specific CD8-positive memory T cells and protective immunity. Hum Gene Ther. 2004, 15(2): 167-77.
    [128] Kinchington P, et al. Virion association of IE62, the varicella-zoster virus (VZV) major transcriptional regulatory protein, requires expression of the VZV open reading frame 66 protein kinase. J. Virol. 2001, 75: 9106-9113.
    [129] Kingham B F, et al. The genome of herpesvirus of turkeys: comparative analysis with Marek's disease viruses. J Gen Virol. 2001, 82(5): 1123-35.
    [130] Klupp B G, et al. Primary envelopment of pseudorabies virus at the nuclear membrane requires the UL34 gene product. J. Virol. 2000, 74: 10063-10071.
    [131] Kodihalli S, et al. Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines. Vaccine. 2000, 18(23): 2592-9.
    [132] Kong B, et al. Efficacy of lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer. In Vivo. 2003, 17(2): 153-6.
    [133] Koptidesova D, et al. Identification and characterization of a cDNA clone derived from the Marek's disease tumour cell line RPL1 encoding a homologue of alpha-transinducing factor (VP16) of HSV-1. Arch Virol. 1995, 140(2): 355-62.
    [134] Kotsakis A, et al. Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein. J Virol. 2001, 75(18): 8697-711.
    [135] Kretz A, et al. HSV-1 VP22 augments adenoviral gene transfer to CNS neurons in the retina and striatum in vivo. Mol Ther. 2003, 7(51): 659-69.
    [136] Kristie T M, et al. The octamer-binding proteins form multi-protein-DNA complexes with the HSV alpha TIF regulatory protein. EMBO J. 1989, 8: 4229-4238.
    [137] Kristie T M, Sharp P A. Interaction of the Oct-1 POU subdomains with specific DNA sequences and with the HSV alpha-trans-activator protein. Genes Dev. 1990, 4: 2383-2396.
    [138] Kristie T M, Sharp P A. Purification of the cellular Cl factor required for the stable recognition of the Oct-1 home-odomain by the herpes simplex virus a-trans-induction factor (VP16). J. Biol. Chem. 1993, 268: 6525-34.
    [139] Kueltzo L A, et al. Conformational lability of herpesvirus protein VP22. J Biol Chem. 2000, 275(43): 33213-21.
    [140] LaBoissiere S, et al. Characterization and transcript mapping of a bovine herpesvirus type 1 gene encoding a polypeptide homologous to the herpes simplex virus type 1 major tegument proteins VP13/14. J Gen Virol. 1992, 73 (11): 2941-7.
    [141] Lai Z, et al. Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors. PNAS. 2000, 97(21): 11297-302.
    [142] Lee K C, et al. Fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit. Gene Ther. 2006, 13(2): 127-37.
    [143] Leopardi L, et al. Repression of the herpes simplex virus type 1 alpha 4 gene by its gene product ( ICP4) within the context of the viral genome is conditioned by the distance and steroaxial alignment of the ICP4 binding site relative to the TATA box. J Virol. 1995, 69: 3042-3048.
    [144] Leslie J, et al. Overexpression of the herpes simplex virus type 1 tegument protein VP22 increases its incorporation into virus particles. Virology. 1996, 220(1): 60-8.
    [145] Letoha, et al. Membrane translocation of penetratin and its derivatives in different cell lines. J. Mol. Recognit. 2003, 16: 272–279.
    [146] Li J R, et al. Enhancement of the immunogenicity of DNA vaccine against infectious bursal disease virus by co-delivery with plasmid encoding chicken interleukin 2. Virology. 2004, 329: 89– 100.
    [147] Li J R, et al. Plasmid DNA encoding antigens of infectious bursal disease viruses induce protective immune responses in chickens: factors influencing efficacy. Virus Research. 2003, 98: 63–74.
    [148] Li Y, et al. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998, 95(9): 4864-9.
    [149] Liang X, et al. Characterization of bovine herpesvirus 1 UL49 homolog gene and product: bovine herpesvirus 1 UL49 homolog is dispensable for virus growth. J Virol. 1995, 69(6): 3863-7.
    [150] Liang X, et al. Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle. Vaccine. 1997, 15(10): 1057-64.
    [151] Lin Y S, et al. Binding of general transcription factor TFIIB to an acidic activating region. Nature. 1991, 353(6344): 569-71.
    [152] Lisa E P, John B. Assembly of infectious herpes simplex virus Type 1 virions in the absence of full-length VP22. J.Vrol. 2000, 74(21): 10041-10054.
    [153] Lisa P L, Blaho J A. Modified VP22 localizes to the cell nucleus during synchronized herpes simplex virus type 1 infection. J Virol. 1999, 73(8): 6769-81.
    [154] Liu C S, et al. VP22 enhanced intercellular trafficking of HSV thymidine kinase reduced the level of ganciclovir needed to cause suicide cell death. J Gene Med. 2001, 3(2): 145-52.
    [155] Luckow V A, et al. Baculovirus systems for the expression of human gene products. Curr. Opin. Biotechnol. 1993, 4: 564.
    [156] Luft F C. Can VP22 resurrect gene therapy? J Mol Med. 1999, 77(8): 575-6.
    [157] Lundberg M, Johansson M. Is VP22 nuclear homing an artifact? Nat Biotechnol. 2001, 19(8): 713-4.
    [158] Lundberg M, Johansson M. Positively charged DNA-binding proteins cause apparent cell membrane translocation. Biochem Biophys Res Commun. 2002, 291(2): 367-71.
    [159] Lyman M G, et al. The attenuated pseudorabies virus strain Bartha fails to package the tegument proteins Us3 and VP22. J Virol. 2003, 77(2): 1403-14.
    [160] Mackem S, Roizman B. Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation of chimeric thymidine kinase genes. J. Virol. 1982, 44: 939-949.
    [161] Macreadie I G, et al. Passive protection against infectious bursal disease virus by viral VP2 expressed in yeast. Vaccine. 1990, 8(6): 549-52.
    [162] Mathias L, et al. Cell surface adherence and endocytosis of protein transduction domains. Mol Ther. 2003, 8(1): 143-50.
    [163] McGeoch D J, et al. The complete DNA sequence of the long unique region in the genome of the herpes simplex virus type 1. J Gen Virol. 1988, 69: 1531-1574.
    [164] McKnight J L, et al. Binding of the virion protein mediating alpha gene induction in herpes simplex virus 1-infected cells to its cis site requires cellular proteins. Proc. Natl. Acad. Sci. USA. 1987, 84: 7061-7065.
    [165] McKnight J L, et al. An 85-kilodalton herpes simplex virus type 1 alpha trans-induction factor (VP16)-VP13/14 fusion protein retains the transactivation and structural properties of the wild-type molecule during virus infection. J Virol. 1994, 68(3): 1750-7.
    [166] McLean C, et al. Monoclonal antibodies to three nonglycosylated antigens of herpes simplex virus type 2. J. Gen. Virol. 1982, 63: 297-305.
    [167] McNabb D, Courtney R J. Characterization of the large tegument protein (ICP1/2) of herpes simplex virus type 1. Virology. 1992, 190: 221-232.
    [168] McLauchlan J. The abundance of the herpes simplex virus type 1 UL37 tegument protein in virus particles is closely controlled. J Gen Virol. 1997, 78 (1): 189-94.
    [169] Mears W E, Rice S A. The herpes simplex virus immediate-early protein ICP27 shuttles between nucleus and cytoplasm. Virology. 1998, 242(1): 128-37.
    [170] Meredith D M, et al. Post-translational modification of the tegument proteins (VP13 and VP14) of herpes simplex virus type 1 by glycosylation and phosphorylation. J Gen Virol. 1991, 72 (11): 2771-5.
    [171] Misra V, et al. The bovine herpesvirus alpha gene transinducing factor activates transcription by mech2 anisms different from those of its HSV-1 counterpart VP16. J Virol. 1995, 69: 5209-5216.
    [172] Mitchell D J, et al. Polyarginine enters cells more efficiently than other polycationic homopolymers. J. Pept. Res. 2000, 56, 318-325.
    [173] Morency E, et al. The protein ICP0 of herpes simplex virus type 1 is targeted to nucleoli of infected cells. Brief report. Arch Virol. 2005, 150(11): 2387-95.
    [174] Morris M C, et al. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat Biotechnol. 2001, 19(12): 1173-6.
    [175] Morris S J, et al. Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role. Arch Virol. 2002, 147(5): 961-79.
    [176] Morrison E, et al. Differences in the intracellular localization and fate of herpes simplex virus tegument proteins early in the infection of Vero cells. J Gen Virol. 1998, 79 (10): 2517-28.
    [177] Morrison E E, et al. Phosphorylation of structural components promotes dissociation of the herpes simplex virus type 1 tegument. J Virol. 1998, 72(9): 7108-14.
    [178] Morse L S, et al. Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 x HSV-2 recombinants. J. Virol. 1978, 26: 389-410.
    [179] Mouzakitis G, et al. Characterization of VP22 in herpes simplex virus-infected cells. J Virol. 2005, 79(19): 12185-98.
    [180] Murphy A L, Murphy S J. Catch VP22: the hitch-hiker's ride to gene therapy? Gene Ther. 1999, 6(1): 4-5.
    [181] Mwangi W, et al. Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote intercellular spreading following initial transfection. J Leukoc Biol. 2005, 78(2): 401-11.
    [182] Nakielny S, Dreyfuss G. Nuclear export of proteins and RNAs. Curr Opin Cell Biol, 1997. 9: 420–429.
    [183] Nakielny S, Dreyfuss G. Nuclear export of proteins and RNAs. Curr Opin Cell Biol. 1997, 9(3): 420-9.
    [184] Naldinho-Souto R, et al. Herpes simplex virus tegument protein VP16 is a component of primary enveloped virions. J Virol. 2006, 80(5): 2582-4.
    [185] Nathalie S, et al. Canine Distemper Virus DNA Vaccination Induces Humoral and Cellular Immunity and Protects against a Lethal Intracerebral Challenge. J. Virol. 1998, 72(11): 8472-76.
    [186] Ng T, et al. UL13 protein kinase of herpes simplex virus 1 complexes with glycoprotein E and mediates the phosphorylation of the viral Fc receptor: glycoproteins E and I. Virology. 1998, 241: 37-48.
    [187] Nikolaus O, et al. Marek’s disease virus: from miasma to model. Nature Reviews (Microbiol). 2006, 4: 283-294.
    [188] Noguchi H, Matsumoto S. Protein transduction technology: a novel therapeutic perspective. Acta Med Okayama. 2006, 60(1): 1-11.
    [189] Normand N, et al. Particle formation by a conserved domain of the herpes simplex virus protein VP22 facilitating protein and nucleic acid delivery. J Biol Chem. 2001, 276(18): 15042-50.
    [190] Normand N, et al. VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. Mol Vis. 2005, 11: 184-91.
    [191] O'Donnell L A, et al. Marek's disease virus VP22: subcellular localization and characterization of carboxyl terminal deletion Mutations. Virolog, 2002, 292(2): 235-40.
    [192] Ogle W O, et al. The UL13 protein kinase and the infected cell type are determinants of posttranslational modification of ICP0. Virology. 1997, 235(2): 406-13.
    [193] Oh Y K, et al. Prolonged organ retention and safety of plasmid DNA administered in polyenthylenimine complexes. Gene Ther. 2001, 8: 1587.
    [194] Oliveira S C, et al. A genetic immunization adjuvant system based on BVP22-antigen fusion. Hum Gene Ther. 2001, 12(10): 1353-9.
    [195] Oppling V, et al. Heterogeneity of the antigenic site responsible for the induction of neutralizing antibodies in infectious bursal disease virus. Arch Virol. 1991, 119(3-4): 211-23.
    [196] Osen W, et al. DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity. Vaccine. 2001, 19(30): 4276-86.
    [197] Oshima S, et al. Charaterization of the UL16 gene product of herpes simplex virus type 2. Arch. Virol. 1998, 143: 863-880.
    [198] Overton H, et al. Herpes simplex virus type 1 gene UL13 encodes a phosphoprotein that is a component of thevirion. Virology. 1992, 190: 184-192.
    [199] Overton H, et al. Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene. Virology. 1994, 202: 97-106.
    [200] Pardoll D M, et al. Exposing the immunology of naked DNA vaccines. Immunity. 1995, 3(2): 165-9.
    [201] Perkins S D, et al. VP22 enhances antibody responses from DNA vaccines but not by intercellular spread. Vaccine. 2005, 23(16): 1931-40.
    [202] Perkins S D, et al. Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax. Genet Vaccines Ther. 2005, 3(1): 3.
    [203] Persson D, et al. Application of a novel analysis to measure the binding. of the membrane-translocating peptide penetratin to negatively. charged liposomes. Biochemistry. 2003, 42: 421-429.
    [204] Phelan A, et al. Intercellular delivery of functional p53 by the herpesvirus protein VP22. Nat Biotechnol. 1998, 16(5): 440-3.
    [205] Pitcovski J, et al. Insect cell-derived VP2 of infectious bursal disease virus confers protection against the disease in chickens. Avian Dis. 1996, 40(4): 753-61.
    [206] Potel C, Elliott G. Phosphorylation of the herpes simplex virus tegument protein VP22 has no effect on incorporation of VP22 into the virus but is involved in optimal expression and virion packaging of ICP0. J Virol. 2005, 79(22): 14057-68.
    [207] Preston C M, et al. Analysis of DNA sequences which regulate the transcription of a herpes simplex virus immediate early gene. J. Virol. 1984, 50: 708-716.
    [208] Purves F C, et al. Herpes simplex virus 1 protein kinase is encoded by open reading frame US3 which is not essential for virus growth in cell culture. J. Virol. 1987, 61: 2896-2901.
    [209] Purves F, et al. UL34, the target of the herpes simplex virus Us3 protein kinase, is a membrane protein which in its unphosphorylated state associates with novel phosphoproteins. J. Virol. 1992, 66: 4295-4303.
    [210] Qiu Z, et al. Bovine herpesvirus tegument protein VP22 enhances thymidine kinase/ganciclovir suicide gene therapy for neuroblastomas compared to herpes simplex virus VP22. J Virol. 2004, 78(8): 4224-33.
    [211] Qiu Z, et al. Bovine herpesvirus VP22 induces apoptosis in neuroblastoma cells by upregulating the expression ratio of Bax to Bcl-2. Hum Gene Ther. 2005, 16(1): 101-8.
    [212] Reddy S M, et al. Identification and structural analysis of a MDV gene encoding a protein kinase. Acta Virol. 1999, 43(2-3): 174-80.
    [213] Ren X, et al. Tyrosine phosphorylation of bovine herpesvirus 1 tegument protein VP22 correlates with the incorporation of VP22 into virions. J. Virol. 2001, 75: 9010-9017.
    [214] Ren X, et al. Bovine herpesvirus 1 tegument protein VP22 interacts with histones, and the carboxyl terminus of VP22 is required for nuclear localization. J Virol. 2001, 75(17): 8251-8.
    [215] Reynolds A, et al. UL31 and UL34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids. J. Virol. 2001, 75: 8803-8817.
    [216] Rixon F J. Structure and assembly of herpesviruses. Semin. Virol. 1993, 4: 135-144.
    [217] Roeder G E, et al. Herpes simplex virus VP22-human papillomavirus E2 fusion proteins produced in mammalian or bacterial cells enter mammalian cells and induce apoptotic cell death. Biotechnol Appl Biochem. 2004, 40(2): 157-65.
    [218] Roizman B, Knipe D. Herpes simplex viruses and their replication. 2001. 2399-2460. In D. Knipe and P. M. Howley (ed.), Fields virology, 4th ed. Lippincott-Raven Publishers, Philadelphia, Pa.
    [219] Roizman B. Herpesviridae, In: Virology, 2nd edition, Fields B N and Knipe M D eds, New York: Raven Press Ltd, 1990, 1787-1887.
    [220] Roller R, et al. Herpes simplex virus type 1 UL34 gene product is required for viral envelopment. J. Virol. 2000, 74: 117-129.
    [221] Roy I, et al. Efficient translocation and apoptosis induction by adenovirus encoded VP22-p53 fusion protein in human tumor cells in vitro. Anticancer Res. 2002, 22(6A): 3185-9.
    [222] Roy V, et al. Direct evidence for the absence of intercellular trafficking of VP22 fused to GFP or to the herpes simplex virus thymidine kinase. Gene Ther. 2005, 12(2): 169-76.
    [223] Saskia A R, et al. Induction of insolubility by herpes simplex virus VP22 precludes intercellular trafficking ofN-terminal Apoptin-VP22 fusion proteins. J. Mol. Med. 2003, 81: 558~565.
    [224] Schwartz J J, Zhang S. Peptide-mediated cellular delivery. Curr Opin Mol Ther. 2000, 2(2): 162-7.
    [225] Schwarze S, et al. In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science. 1999, 285: 1569–1572.
    [226] Sciortino M T, et al. Of the three tegument proteins that package mRNA in herpes simplex virions, one (VP22) transports the mRNA to uninfected cells for expression prior to viral infection. Proc Natl Acad Sci U S A. 2002, 99(12): 8318-23.
    [227] Sharma K, et al. Molecular characterization of infectious bursal disease virus isolates from Nepal based on hypervariable region of VP2 gene. Acta Virol. 2005, 49(1): 59-64.
    [228] Shedlock D J, et al. DNA vaccination: antigen presentation and the induction of immunity. J Leukoc Biol. 2000, 68(6): 793-806.
    [229] Sheridan P J, et al. VP22-mediated intercellular transport correlates with enhanced biological activity of MybEngrailed but not (HSV-I) thymidine kinase fusion proteins in primary vascular cells following non-viral transfection. J Gene Med. 2005, 7(3): 375-85.
    [230] Shibaki T, et al. Participation of type I interferon in the decreased virulence of the UL13 gene-deleted mutant of herpes simplex virus type 1. J Interferon Cytokine Res. 2001, 21(5): 279-85.
    [231] Siomi H, et al. Effects of a highly basic region of human immunodeficiency virus Tat protein on nucleolar localization. J Virol. 1990, 64(4): 1803–1807.
    [232] Siomi H, et al. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988, 55(2): 197–209.
    [233] Silverman N, et al. Yeast ADA2 protein binds to the VP16 protein activation domain and activates transcription. Proc Natl Acad Sci U S A. 1994, 91(24): 11665-8.
    [234] Soden J, et al. Genetic engineering of the glucocorticoid receptor by fusion with the herpes viral protein VP22 causes selective loss of transactivation. J Endocrinol. 2002, 172(3): 615-25.
    [235] Spear P G. Entry of alpha herpesviruses into cells. Semin. Virol. 1993, 4: 167-180.
    [236] Spear P G and Roizman B. Proteins specified by herpes simplex virus. V. Purification and structural proteins of the herpes virion. J. Virol. 1972, 9: 143-159.
    [237] Stephen F, et al. Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci USA, 1994, 91: 664~668
    [238] Stringer K F, et al. Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990, 345(6278): 783-6.
    [239] Stuart D P, et al. Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax. Genet Vaccines Ther. 2005, 3: 3.
    [240] Stroh C, et al. Specific inhibition of transcription factor NF-kappaB through intracellular protein delivery of I kappaBalpha by the Herpes virus protein VP22. Oncogene. 2003, 22(34): 5367-73.
    [241] Subramaniam P S, et al. The carboxyl terminus of interferon-gamma contains a functional polybasic nuclear localization sequence. J Biol Chem. 1999, 274(1): 403-7.
    [242] Suzuki K, et al. Enhanced effect of myocardial gene transfection by VP22-mediated intercellular protein transport. J Mol Cell Cardiol. 2004, 36(4): 603-6.
    [243] Tadahiko I, et al. Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton. Science. 2003, 299(5613): 1713-1716.
    [244] Takauwa H, et al. Herpes simplex virus encodes a virion-assoiated protein which promoters long cellular processes in over-expressing cell. Genes Cells, 2001, 6: 955-966.
    [245] Tanimura N, et al. Appearance of T cells in the bursa of Fabricius and cecal tonsils during the acute phase of infectious bursal disease virus infection in chickens. Avian Dis. 1997, 41(3): 638-45.
    [246] T. del Rio, et al. The pseudorabies virus VP22 homologue (UL49) is dispensable for virus growth in vitro and has no effect on virulence and neuronal spread in rodents. J. Virol. 2002, 76(2): 774-782.
    [247] Thomas S. Might a vanguard of mRNAs prepare cells for the arrival of herpes simplex virus? PNAS. 2002, 99(13): 8465–8466.
    [248] Torchilin V P, et al. TAT peptide on the surface of liposomes affords their efficient intracellular delivery even atlow temperature and in the presence of metabolic inhibitors. PNAS. 2001, 8(15): 8786-8791.
    [249] Triezenberg S J, et al. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988, 2: 718–729.
    [250] Trus B, et al. Capsid structure of simian cytomegalovirus from cryoelectron microscopy: evidence for tegument attachment sites. J. Virol. 1999, 73: 2181-2192.
    [251] Tsein R Y. The green fluorescent protein. Annu. Rev. Biochem. 1998, 67: 509-544.
    [252] Tulman E R, et al. The genome of a very virulent Marek's disease virus. J Virol. 2000, 74(17): 7980-8.
    [253] Tyagi M, et al. Internalization of HIV1 Tat requires cell surface heparan sulfate proteoglycans. J Biol Chem, 2001, 276(5):3254-3261.
    [254] Vakharia V N, et al. Active and passive protection against variant and classic infectious bursal disease virus strains induced by baculovirus-expressed structural proteins. Vaccine. 1994, 12(5): 452-6.
    [255] Vakharia V N, et al. Infectious bursal disease virus structural proteins expressed in a baculovirus recombinant confer protection in chickens. J Gen Virol. 1993, 74(6): 1201-6.
    [256] Van Drunen LHS, et al. The role of the major tegument protein VP8 of bovine herpesvirus-1 in infection and immunity. Virology. 1995, 206(1): 413-25.
    [257] van Leeuwen H, et al. Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT. J Gen Virol. 2003, 84(9): 2501-10.
    [258] van Drunen Littel-van den Hurk S, et al. The role of the major tegument protein VP8 of bovine herpesvirus-1 in infection and immunity. Virology. 1995, 206(1): 413-25.
    [259] Wadia J S, et al. Apoptin/VP3 contains a concentration-dependent nuclear localization signal (NLS), not a tumorigenic selective NLS. J Virol. 2004, 78(11): 6077-8.
    [260] Wadia J S, et al. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med. 2004, 10(3): 310-5.
    [261] Walter F, et al. Physical interaction between envelope glycoproteins E and M of Pseudorabies virus and the major tegument protein UL49. J. Virol, 2002, 76(16): 8208-8217.
    [262] Wang X Q, et al. Efficacy of DNA vaccines against IBDV in chickens enhanced by coadministration with CpG oligodeoxynucleotide. Avian Dis. 2003, 47: 1305-12.
    [263] Weinheimer S P, et al. Deletion of the VP16 open reading frame of herpes simplex virus type 1. J. Virol. 1992, 66: 258-269.
    [264] Weitzman M D. VP22 flips the switch on cell death. Mol Ther. 2003, 7(2): 146-7.
    [265] Wender P A, et al. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13003-8.
    [266] Williams A E and Davison T F. Enhanced immunopathology induced by very virulent infectious bursal disease virus. Avian Path. 2005, 34(11): 4-14.
    [267] Wills K N, et al. Intratumoral spread and increased efficacy of a p53-VP22 fusion protein expressed by a recombinant adenovirus. J Virol. 2001, 75(18): 8733-41.
    [268] Wu P C, et al. Secreted expression of the VP2 protein of very virulent infectious bursal disease virus in the methylotrophic yeast Pichia pastoris. J. Virol. Methods. 2005, 123(2): 221-5.
    [269] Wybranietz W A, et al. Quantification of VP22-GFP spread by direct fluorescence in 15 commonly used cell lines. J Gene Med. 1999, 1(4): 265-74.
    [270] Wybranietz W A, et al. Enhanced suicide gene effect by adenoviral transduction of a VP22-cytosine deaminase (CD) fusion gene. Gene Ther. 2001, 8(21): 1654-64.
    [271] Xiao P and Capone J P. A cellular factor binds to the herpes simplex virus type 1 transactivator Vmw65 and is required for Vmw65-dependent protein-DNA complex assembly with Oct-1. Mol. Cell. Biol. 1990, 10: 4974-4977.
    [272] Yamamoto S, et al. Two novel genes of herpes simplex virus type 1 involved in cell fusion. Kurume Med J. 1993, 40(4): 169-75.
    [273] Yanagida N, et al. Nucleotide and predicted amino acid sequences of Marek's disease virus homologues of herpes simplex virus major tegument proteins. J. Gen. Virol. 1993, 74 (9): 1837-1845.
    [274] Yao F and Courtney R J. A major transcriptional regulatory protein (ICP4) of herpes simplex virus type 1 is associated with purified virions. J. Virol. 1989, 63: 3338-3344.
    [275] Yao F, et al. Association of ICP0 but not ICP27 with purified virions of herpes simplex virus type 1. J Virol. 1992, 66(5): 2709-16.
    [276] Yedowitz J C, et al. Nuclear localizations of the herpes simplex virus type 1 tegument proteins VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization and VP22 nuclear import. J Virol. 2005, 79(8): 4730-43.
    [277] Ye G J and Roizman B. The essential protein encoded by the UL31 gene of herpes simplex virus 1 depends for its stability on the presence of the UL34 protein. Proc. Natl. Acad. Sci. USA. 2000, 97: 11002-11007.
    [278] Ye D, et al. Evaluation of strategies for the intracellular delivery of proteins. Pharm Res. 2002, 19(9): 1302-9.
    [279] Yi J, et al. VP22 fusion protein-based dominant negative mutant can inhibit hepatitis B virus replication. World J Gastroenterol. 2005, 11(41): 6429-32.
    [280] Yuen L, Moss B. Oligonucleotide sequence signaling transcriptional termination of vaccinia virus early genes. Proc Natl Acad Sci U S A. 1987, 84(18): 6417-21.
    [281] Zavaglia D, et al. VP22-mediated and light-activated delivery of an anti-c-raf1 antisense oligonucleotide improves its activity after intratumoral injection in nude mice. Mol Ther. 2003, 8(5): 840-5.
    [282] Zavaglia D, et al. Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered p27-VP22 fusion protein. Gene Ther. 2003, 10(4): 314-25.
    [283] Zavaglia D, et al. VP22-mediated and light-activated delivery of an anti-c-raf1 antisense oligonucleotide improves its activity after intratumoral injection in nude mice. Mol Ther. 2003, 8(5): 840-5.
    [284] Zavaglia D, et al. Poor intercellular transport and absence of enhanced antiproliferative activity after non-viral gene transfer of VP22-P53 or P53-VP22 fusions into p53 null cell lines in vitro or in vivo. J Gene Med. 2005, 7(7): 936-44.
    [285] Zhang Y, et al. Herpes simplex virus type 1 UL46 and UL47 deletion mutants lack VP11 and VP12 or VP13 and VP14, respectively, and exhibit altered viral thymidine kinase expression. J. Virol. 1993, 67(3): 1482-92.
    [286] Zender L, et al. Gene therapy by intrahepatic and intratumoral trafficking of p53-VP22 induces regression of liver tumors. Gastroenterology. 2002, 123(2): 608-18.
    [287] Zender L, et al. VP22-mediated intercellular transport of p53 in hepatoma cells in vitro and in vivo. Cancer Gene Ther. 2002, 9(6): 489-96.
    [288] Zheng C, et al. Characterization of the nuclear localization and nuclear export signals of bovine herpesvirus 1 VP22. J Virol. 2005, 79(18): 11864-72.
    [289] Zheng C, et al. Bovine herpesvirus 1 VP22 enhances the efficacy of a DNA vaccine in cattle. J Virol. 2005, 79(3): 1948-53.
    [290] Zheng C, et al. Intercellular trafficking of the major tegument protein VP22 of bovine herpesvirus-1 and its application to improve a DNA vaccine. Arch Virol. 2006, 151(5): 985-93.
    [291] Zhu G S, et al. Marek's disease virus type 1-specific phosphorylated proteins pp38 and pp24 with common amino acid termini are encoded from the opposite junction regions between the long unique and inverted repeat sequences of viral genome. Virology. 1994 May 1;200(2):816-20.
    [292] Zhu J, et al. Nuclear and mitochondrial localization signals overlap within bovine herpesvirus 1 tegument protein VP22. J Biol Chem. 2005, 280(16): 16038-44.
    [293] Zhu W and Courtney R. Chemical cross-linking of virion envelope and tegument proteins of herpes simplex virus type 1. Virology. 1994, 204: 590-599.
    [294] Zhu Z, et al. Co-operativity among herpes simplex virus type 1 immediate-early regulatory proteins: ICP4 and ICP27 affect the intracellular localization of ICP0. J Virol. 1994, 68: 3027-3040.
    [295] Zhu Z, Schaffer P A. Intracellular localization of the herpes simplex virus type 1 major transcriptional regulatory protein, ICP4, is affected by ICP27. J Virol. 1995, 69: 49-59.
    [296] Zhou Z H, et al. Visualization of Tegument-Capsid Interactions and DNA in Intact Herpes Simplex Virus Type 1Virions. J. Virol. 1999, 73(4): 3210-3218.
    [297] F. 奥斯伯等著(颜子颖,王海林译).精编分子生物学实验指南.科学出版社.1998.658-676.
    [298] 陈鸿军, 等. MDV CVI988/Rispens弱毒株VP22基因克隆和序列分析.扬州大学学报(农业与生命科学版).2003, 24 (4): 7-10.
    [299] 陈鸿军, 等. 马立克氏病病毒CVI988弱毒株体外感染期间VP22的表达和细胞间转导作用.中国科学C辑. 2006, 26(2): 145-149.
    [300] 陈鸿军, 等. MDV-1 VP22羧基端在大肠杆菌中高效可溶性表达.中国病毒学. 2006, 21(2): 284-286.
    [301] 陈任安. PTD-bcr/abl融合蛋白的表达及其对K562细胞生长的影响.第四军医大学学位论文.2002.
    [302] 陈希文, 等. 基因枪与肌肉注射猪繁殖与呼吸综合征病毒ORF5基因疫苗诱导小鼠体液及细胞免疫的比较研究. 畜牧兽医学报. 2005, 36(8): 812-818.
    [303] 丁劲. TAT-乙肝病毒靶向核糖核酸酶的表达纯化及其抗病毒活性的初步研究. 第四军医大学学位论文.2003
    [304] 方忠意. 脊椎动物病毒分类的新变化. http://www.bbioo.com/blife/microbio/virus/200510/3386.html.
    [305] 甘孟候. 禽流感.中国农业出版社.2004
    [306] 戴建华, 等. 鸡γ-干扰素基因的克隆及其在原核和真核表达系统中的表达. 中国预防兽医学报. 2003, 25(4): 249-53.
    [307] 刘强. PTD介导BCR/ABL蛋白细胞转导及免疫原性的研究. 第四军医大学学位论文.2003.
    [308] 刘秀梵. 单克隆抗体技术及其在农业中的应用.1994.
    [309] 刘岳龙.鸡贫血病毒中国株基因序列比较、病毒编码蛋白的表达及分子克隆化病毒的构建 .扬州大学博士论文. 2001.
    [310] 鲁润龙. 细胞生存、死亡与癌变. 合肥: 中国科学技术大学出版社. 1996.
    [311] 马道新, 等. VP22增强人巨细胞病毒pp65核酸疫苗在小鼠体内免疫活性的实验研究. 医学杂志.2005, 85(15):1049-52.
    [312] 彭 涛, 等. 体内蛋白转导的研究进展.中国药科大学学报.2003, 34(5): 477-480.
    [313] 秦爱建. 禽白血病病毒J亚群囊膜糖蛋白基因的生物学和生物化学特性. 扬州大学博士论文. 1999.
    [314] 瞿素, 等. HSV-1 VP22和hlL-18增强HBV DNA微球疫苗诱导的小鼠体液免疫应答.现代免疫学. 2005年, 25(4): 300-304.
    [315] 宋云峰, 等. 猪 2 型圆环病毒核酸疫苗免疫效应研究.畜牧兽医学报. 2005, 36(10): 1049-54.
    [316] 韦平. 马立克氏病病毒meq基因的功能研究.扬州大学博士论文.2002.
    [317] 肖少波. 伪狂犬病毒 gC 基因“自杀性”DNA 疫苗及 VP22 蛋白转导的免疫增强效应研究.华中农业大学博士论文.2004.
    [318] 余传霖, 熊思东. 分子免疫学. 上海医科大学出版社. 2001.
    [319] 徐耀先, 等. 病毒命名与分类系统研究进展.中国病毒学.1999, 14(3): 200-204.
    [320] 薛庆善.体外培养的原理与技术.科学出版社.2001.
    [321] 杨茂, 等. 单纯疱疹病毒Ⅰ型基因表达调控研究的进展.病毒学报. 1997, 13(4): .
    [322] 杨峰山. 抗 Bt 小菜蛾的选育、受体基因克隆及 PTD 对 Cry1Ac 的增效作用.中国农业大学博士论文.2004.
    [323] 赵武, 等. 牛疱疹病毒I型VP22和猪繁殖与呼吸综合征病毒GP5融合基因DNA疫苗的免疫效应. 2005, 2l(5): 725-28.

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