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HSV trafficking and development of gene therapy vectors with applications in the nervous system

Gene Therapy volume 12, pages 891–901 (2005)Cite this article

Abstract

Herpes simplex virus type 1 (HSV-1) is a neurotropic double-stranded DNA virus that causes cold sores, keratitis, and rarely encephalitis in humans. Nonpathogenic HSV-1 gene transfer vectors have been generated by elimination of viral functions necessary for replication. The life cycle of the native virus includes replication in epithelial cells at the site of initial inoculation followed by retrograde axonal transport to the nuclei of sensory neurons innervating the area of cutaneous primary infection. In this review, we summarize the current understanding of the molecular basis for HSV cell entry, nuclear transport of the genome, virion egress following replication, and retrograde and anterograde axonal transport in neurons. We discuss how each of these properties has been exploited or modified to allow the generation of gene transfer vectors with particular utility for neurological applications. Recent advances in engineering virus entry have provided proof of principle that vector targeting is possible. Furthermore, significant and potentially therapeutic modifications to the pathological responses to various noxious insults have been demonstrated in models of peripheral nerve disease. These applications exploit the natural axonal transport mechanism of HSV, allowing transgene expression in the cell nucleus within the inaccessible trigeminal ganglion or dorsal root ganglion, following the noninvasive procedure of subcutaneous vector inoculation. These findings demonstrate the importance of understanding basic virology in the design of vector systems and the powerful approach of exploiting favorable properties of the parent virus in the generation of gene transfer vectors.

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References

  1. Homa FL, Brown JC . Capsid assembly and DNA packaging in herpes simplex virus. Rev Med Virol 1997; 7: 107–122.

    Article  CAS  PubMed  Google Scholar 

  2. Steven AC, Spear PG . Herpesvirus capsid assembly and envelopment. In: Chiu W, Burnett R, Garcea R (eds). Structural Biology of Viruses. Oxford University Press: New York, NY, 1997, pp 312–351.

    Google Scholar 

  3. Spear PG . Entry of alphaherpesviruses into cells. Sem Virol 1993b; 4: 167–180.

    Article  CAS  Google Scholar 

  4. Spear P . Membrane fusion induced by herpes simplex virus. In: Bentz J (ed). Viral Fusion Mechanisms. CRC Press: Boca Raton, FL, 1993a, pp 201–232.

    Google Scholar 

  5. Spear PG . Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 2004; 6: 401–410.

    Article  CAS  PubMed  Google Scholar 

  6. Dingwell K et al. Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. J Virol 1994; 68: 834–845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Friedman HM et al. Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature 1984; 309: 633–635.

    Article  CAS  PubMed  Google Scholar 

  8. Friedman HM et al. Immune evasion properties of herpes simplex virus type 1 glycoprotein gC. J Virol 1996; 70: 4253–4260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lubinski JM et al. Herpes simplex virus type 1 evades the effects of antibody and complement in vivo. J Virol 2002; 76: 9232–9241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stern S, Tanaka M, Herr W . The Oct-1 homoeodomain directs formation of a multiprotein–DNA complex with the HSV transactivator VP16. Nature 1989; 341: 624–630.

    Article  CAS  PubMed  Google Scholar 

  11. Wysocka J, Herr W . The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci 2003; 28: 294–304.

    Article  CAS  PubMed  Google Scholar 

  12. Kwong AD, Frenkel N . The herpes simplex virus virion host shutoff function. J Virol 1989; 63: 4834–4839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kwong AD, Kruper JA, Frenkel N . Herpes simplex virus virion host shutoff function. J Virol 1988; 62: 912–921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Granzow H et al. Egress of alphaherpesviruses: comparative ultrastructural study. J Virol 2001; 75: 3675–3684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wisner TW, Johnson DC . Redistribution of cellular and herpes simplex virus proteins from the trans-golgi network to cell junctions without enveloped capsids. J Virol 2004; 78: 11519–11535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Foster TP et al. Overexpression of gK in gK-transformed cells collapses the Golgi apparatus into the endoplasmic reticulum inhibiting virion egress, glycoprotein transport, and virus-induced cell fusion. Virology 2003; 317: 237–252.

    Article  CAS  PubMed  Google Scholar 

  17. Jensen HL, Norrild B . The morphogenesis of herpes simplex virus type 1 in infected parental mouse L fibroblasts and mutant gro29 cells. APMIS 2003; 111: 1037–1052.

    Article  PubMed  Google Scholar 

  18. Jensen HL, Norrild B . Temporal morphogenesis of herpes simplex virus type 1-infected and brefeldin A-treated human fibroblasts. Mol Med 2002; 8: 210–224.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rixon FJ, McNab D . Packaging-competent capsids of a herpes simplex virus temperature-sensitive mutant have properties similar to those of in vitro-assembled procapsids. J Virol 1999; 73: 5714–5721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Trus BL et al. The herpes simplex virus procapsid: structure, conformational changes upon maturation, and roles of the triplex proteins VP19c and VP23 in assembly. J Mol Biol 1996; 263: 447–462.

    Article  CAS  PubMed  Google Scholar 

  21. Newcomb WW et al. Assembly of the herpes simplex virus capsid: characterization of intermediates observed during cell-free capsid formation. J Mol Biol 1996; 263: 432–446.

    Article  CAS  PubMed  Google Scholar 

  22. Chi JH, Wilson DW . ATP-dependent localization of the herpes simplex virus capsid protein VP26 to sites of procapsid maturation. J Virol 2000; 74: 1468–1476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McGeoch DJ, Dolan A, Donald S, Rixon FJ . Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J Mol Biol 1985; 181: 1–13.

    Article  CAS  PubMed  Google Scholar 

  24. McGeoch DJ et al. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 1988; 69: 1531–1574.

    Article  CAS  PubMed  Google Scholar 

  25. McGeoch DJ, Cunningham C, McIntyre G, Dolan A . Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2. J Gen Virol 1991; 72: 3057–3075.

    Article  CAS  PubMed  Google Scholar 

  26. McGeoch DJ, Dolan A, Donald S, Brauer DH . Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res 1986; 14: 1727–1745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Perry LJ, McGeoch DJ . The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 1988; 69 (Part 11): 2831–2846.

    Article  CAS  PubMed  Google Scholar 

  28. Roizman BaK DM . Herpes simplex viruses and their replication. In: KDMaH PM (ed). Fields Virology. Lippincott Williams & Wilkins: Philadelphia, 2001, pp 2399–2459.

    Google Scholar 

  29. Nicola AV, McEvoy AM, Straus SE . Roles for endocytosis and low pH in herpes simplex virus entry into HeLa and Chinese hamster ovary cells. J Virol 2003; 77: 5324–5332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nicola AV, Straus SE . Cellular and viral requirements for rapid endocytic entry of herpes simplex virus. J Virol 2004; 78: 7508–7517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cai W, Gu B, Person S . Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. J Virol 1988; 62: 2596–2604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Desai P, Schaffer P, Minson A . Excretion of non-infectious virus particles lacking glycoprotein H by a temperature-sensitive mutant of herpes-simplex virus type 1: evidence that gH is essential for virion infectivity. J Gen Virol 1988; 69: 1147–1156.

    Article  CAS  PubMed  Google Scholar 

  33. Hutchinson L et al. A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH. J Virol 1992; 66: 2240–2250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ligas M, Johnson D . A herpes simplex virus mutant in which glycoprotein D sequences are replaced by β-galactosidase sequences binds to but is unable to penetrate into cells. J Virol 1988; 62: 1486–1494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ali MA . Oligomerization of herpes simplex virus glycoprotein B occurs in the endoplasmic reticulum and a 102 amino acid cytosolic domain is dispensable for dimer assembly. Virology 1990; 178: 588–592.

    Article  CAS  PubMed  Google Scholar 

  36. Claesson-Welsh L, Spear PG . Oligomerization of herpes simplex virus glycoprotein B. J Virol 1986; 60: 803–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Highlander SL et al. Oligomer formation of the gB glycoprotein of herpes simplex virus type 1. J Virol 1991; 65: 4275–4283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Laquerre S, Person S, Glorioso J . Glycoprotein B of herpes simplex virus type 1 oligomerizes through the intermolecular interaction of a 28 amino acid domain. J Virol 1996; 70: 1640–1650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Qadri I, Gimeno C, Navarro D, Pereira L . Mutations in conformation-dependent domains of herpes simplex virus 1 glycoprotein B affect the antigenic properties, dimerization, and transport of the molecule. Virology 1991; 180: 135–152.

    Article  CAS  PubMed  Google Scholar 

  40. Sarmiento M, Spear PG . Membrane proteins specified by herpes simplex viruses. IV. Conformation of the virion glycoprotein designated VP7(B). J Virol 1979; 29: 1159–1167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Johnson D et al. Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI. J Virol 1988; 62: 1347–1354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Westra DF et al. Glycoprotein H of herpes simplex virus type 1 requires glycoprotein L for transport to the surfaces of insect cells. J Virol 1997; 71: 2285–2291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fuller AO, Lee WC . Herpes simplex virus type 1 entry through a cascade of virus–cell interactions requires different roles of gD and gH in penetration. J Virol 1992; 66: 5002–5012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gruenheid S, Gatzke L, Meadows H, Tufaro F . Herpes simplex virus infection and propagation in a mouse L cell mutant lacking heparan sulfate proteoglycans. J Virol 1993; 67: 93–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Herold B et al. Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulfate and glycoprotein B. J Gen Virol 1994; 75: 1211–1222.

    Article  CAS  PubMed  Google Scholar 

  46. Shih M et al. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol 1992; 116: 1273–1281.

    Article  Google Scholar 

  47. Spear PG et al. Heparan sulfate glycosaminoglycans as primary cell surface receptors for herpes simplex virus. Adv Exp Med Biol 1992; 313: 341–353.

    Article  CAS  PubMed  Google Scholar 

  48. Wudunn D, Spear P . Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol 1989; 63: 52–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Trybala E et al. Glycosaminoglycan-binding ability is a feature of wild-type strains of herpes simplex virus type 1. Virology 2002; 302: 413–419.

    Article  CAS  PubMed  Google Scholar 

  50. Tal-Singer R et al. Interaction of herpes simplex virus glycoprotein gC with mammalian cell surface molecules. J Virol 1995; 69: 4471–4483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Herold BC et al. Identification of structural features of heparin required for inhibition of herpes simplex virus type 1 binding. Virology 1995; 206: 1108–1116.

    Article  CAS  PubMed  Google Scholar 

  52. Li Y, van Drunen Littel-van den Hurk S, Babiuk LA, Liang X . Characterization of cell-binding properties of bovine herpesvirus 1 glycoproteins B, C, and D: identification of a dual cell-binding function of gB. J Virol 1995; 69: 4758–4768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Trybala E et al. Structural and functional features of the polycationic peptide required for inhibition of herpes simplex virus invasion of cells. Antiviral Res 2004; 62: 125–134.

    Article  CAS  PubMed  Google Scholar 

  54. Laquerre S et al. Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread. J Virol 1998; 72: 6119–6130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Laquerre S, Anderson DB, Stolz DB, Glorioso JC . Recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells. J Virol 1998; 72: 9683–9697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Montgomery RI, Warner MS, Lum BJ, Spear PG . Herpes simplex virus 1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 1996; 87: 427–436.

    Article  CAS  PubMed  Google Scholar 

  57. Nicola AV et al. Monoclonal antibodies to distinct sites on herpes simplex virus (HSV) glycoprotein D block HSV binding to HVEM. J Virol 1998; 72: 3595–3601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Dean HJ et al. Single amino acid substitutions in gD of herpes simplex virus 1 confer resistance to gD-mediated interference and cause cell-type-dependent alterations in infectivity. Virology 1994; 199: 67–80.

    Article  CAS  PubMed  Google Scholar 

  59. Connolly SA et al. Structure-based analysis of the herpes simplex virus glycoprotein D binding site present on herpesvirus entry mediator HveA (HVEM). J Virol 2002; 76: 10894–10904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Carfi A et al. Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol Cell 2001; 8: 169–179.

    Article  CAS  PubMed  Google Scholar 

  61. Warner MS et al. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology 1998; 246: 179–189.

    Article  CAS  PubMed  Google Scholar 

  62. Shukla D et al. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 1999; 99: 13–22.

    Article  CAS  PubMed  Google Scholar 

  63. Geraghty RJ et al. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 1998; 280: 1618–1620.

    Article  CAS  PubMed  Google Scholar 

  64. Mata M, Zhang M, Hu X, Fink DJ . HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons, of the rat peripheral nervous system. J Neurovirol 2001; 7: 476–480.

    Article  CAS  PubMed  Google Scholar 

  65. Haarr L et al. Transcription from the gene encoding the herpesvirus entry receptor nectin-1 (HveC) in nervous tissue of adult mouse. Virology 2001; 287: 301–309.

    Article  CAS  PubMed  Google Scholar 

  66. Richart SM et al. Entry of herpes simplex virus type 1 into primary sensory neurons in vitro is mediated by Nectin-1/HveC. J Virol 2003; 77: 3307–3311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Krummenacher C et al. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. J Virol 1998; 72: 7064–7074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Krummenacher C et al. The first immunoglobulin-like domain of HveC is sufficient to bind herpes simplex virus gD with full affinity, while the third domain is involved in oligomerization of HveC. J Virol 1999; 73: 8127–8137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Manoj S et al. Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism. Proc Natl Acad Sci USA 2004; 101: 12414–12421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Fuller AO, Spear PG . Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies. J Virol 1985; 55: 475–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Highlander SL et al. Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein D inhibit virus penetration. J Virol 1987; 61: 3356–3364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Forrester A et al. Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. J Virol 1992; 66: 341–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Roop C, Hutchinson L, Johnson D . A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H. J Virol 1993; 67: 2285–2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cai W et al. Linker-insertion nonsense and restriction-site deletion mutations of the gB glycoprotein gene of herpes simplex virus type 1. J Virol 1987; 61: 714–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Cai WH, Gu B, Person S . Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. J Virol 1988; 62: 2596–2604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Turner A, Bruun B, Minson T, Browne H . Glycoproteins gB, gD, and gHgL of herpes simplex virus type 1 are necessary and sufficient to mediate membrane fusion in a Cos cell transfection system. J Virol 1998; 72: 873–875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dingwell KS, Doering LC, Johnson DC . Glycoproteins E and I facilitate neuron-to-neuron spread of herpes simplex virus. J Virol 1995; 69: 7087–7098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sodeik B, Ebersold MW, Helenius A . Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus. J Cell Biol 1997; 136: 1007–1021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Dohner K et al. Function of dynein and dynactin in herpes simplex virus capsid transport. Mol Cell Biol 2002; 13: 2795–2809.

    Article  CAS  Google Scholar 

  80. Mabit H et al. Intact microtubules support adenovirus and herpes simplex virus infections. J Virol 2002; 76: 9962–9971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ye GJ, Vaughan KT, Vallee RB, Roizman B . The herpes simplex virus 1 U(L)34 protein interacts with a cytoplasmic dynein intermediate chain and targets nuclear membrane. J Virol 2000; 74: 1355–1363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ojala PM et al. Herpes simplex virus type 1 entry into host cells: reconstitution of capsid binding and uncoating at the nuclear pore complex in vitro. Mol Cell Biol 2000; 20: 4922–4931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Narayanan A, Nogueira ML, Ruyechan WT, Kristie TM . Combinatorial transcription of HSV and VZV IE genes is strictly determined by the cellular coactivator HCF-1. J Biol Chem 2005; 280: 1369–1375.

    Article  CAS  PubMed  Google Scholar 

  84. Honess R, Roizman B . Regulation of herpes simplex virus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol 1974; 14: 8–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Holland LE, Anderson KP, Shipman C, Wagner EK . Viral DNA synthesis is required for efficient expression of specific herpes simplex virus type 1 mRNA. Virology 1980; 101: 10–24.

    Article  CAS  PubMed  Google Scholar 

  86. Mavromara-Nazos P, Roizman B . Activation of herpes simplex virus 1γ2 genes by viral DNA replication. Virology 1987; 161: 593–598.

    Article  CAS  PubMed  Google Scholar 

  87. Banfield BW, Tufaro F . Herpes simplex virus particles are unable to traverse the secretory pathway in the mouse L-cell mutant gro29. J Virol 1990; 64: 5716–5729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chatterjee S, Sarkar S . Studies on endoplasmic reticulum–golgi complex cycling pathway in herpes simplex virus-infected and brefeldin A-treated human fibroblast cells. Virology 1992; 191: 327–337.

    Article  CAS  PubMed  Google Scholar 

  89. Cheung P, Banfield BW, Tufaro F . Brefeldin A arrests the maturation and egress of herpes simplex virus particles during infection. J Virol 1991; 65: 1893–1904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Serafini-Cessi F, Dall'Olio F, Scannavini M, Campadelli-Fiume G . Processing of herpes simplex virus-1 glycans in cells defective in glycosyl transferases of the Golgi system: relationship to cell fusion and virion egress. Virology 1983; 131: 59–70.

    Article  CAS  PubMed  Google Scholar 

  91. Skepper JN, Whiteley A, Browne H, Minson A . Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment → deenvelopment → reenvelopment pathway. J Virol 2001; 75: 5697–5702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Johnson D, Spear P . Monensin inhibits the processing of herpes simplex virus glycoproteins, their transport to the cell surface, and the egress of virions from infected cells. J Virol 1982; 43: 1102–1112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jones F, Grose C . Role of cytoplasmic vacuoles in varicella-zoster virus glycoprotein trafficking and virion envelopment. J Virol 1988; 62: 2701–2711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Stackpole CW . Herpes-type virus of the frog renal adenocarcinoma. I. Virus development in tumor transplants maintained at low temperature. J Virol 1969; 4: 75–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mettenleiter TC . Herpesvirus assembly and egress. J Virol 2002; 76: 1537–1547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Marchand CF, Schwab ME . Binding, uptake and retrograde axonal transport of herpes virus suis in sympathetic neurons. Brain Res 1986; 383: 262–270.

    Article  CAS  PubMed  Google Scholar 

  97. Lycke E et al. Uptake and transport of herpes simplex virus in neurites of rat dorsal root ganglia cells in culture. J Gen Virol 1984; 65 (Part 1): 55–64.

    Article  PubMed  Google Scholar 

  98. Lycke E et al. Herpes simplex virus infection of the human sensory neuron. An electron microscopy study. Arch Virol 1988; 101: 87–104.

    Article  CAS  PubMed  Google Scholar 

  99. Smith GA, Gross SP, Enquist LW . Herpesviruses use bidirectional fast-axonal transport to spread in sensory neurons. Proc Natl Acad Sci USA 2001; 98: 3466–3470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bearer EL et al. Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. Proc Natl Acad Sci USA 2000; 97: 8146–8150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. LaVail JH et al. Axonal transport and sorting of herpes simplex virus components in a mature mouse visual system. J Virol 2003; 77: 6117–6126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kristensson K et al. Neuritic transport of herpes simplex virus in rat sensory neurons in vitro. Effects of substances interacting with microtubular function and axonal flow [nocodazole, taxol and erythro-9-3-(2-hydroxynonyl)adenine]. J Gen Virol 1986; 67 (Part 9): 2023–2028.

    Article  CAS  PubMed  Google Scholar 

  103. Topp KS, Meade LB, LaVail JH . Microtubule polarity in the peripheral processes of trigeminal ganglion cells: relevance for the retrograde transport of herpes simplex virus. J Neurosci 1994; 14: 318–325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Paschal BM, Vallee RB . Retrograde transport by the microtubule-associated protein MAP 1C. Nature 1987; 330: 181–183.

    Article  CAS  PubMed  Google Scholar 

  105. Mellerick DM, Fraser N . Physical state of the latent herpes simplex virus genome in a mouse model system: evidence suggesting an episomal state. Virology 1987; 158: 265–275.

    Article  CAS  PubMed  Google Scholar 

  106. Croen KD et al. Latent herpes simplex virus in human trigeminal ganlia. Detection of an immediate early gene ‘anti-sense’ transcript by in situ hybridization. N Engl J Med 1987; 317: 1427–1432.

    Article  CAS  PubMed  Google Scholar 

  107. Spivack JG, Fraser NW . Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J Virol 1987; 61: 3841–3847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Stevens JG et al. RNA complementary to a herpesviruses α gene mRNA is prominent in latently infected neurons. Science 1987; 255: 1056–1059.

    Article  Google Scholar 

  109. Rock DL et al. Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. J Virol 1987; 61: 3820–3826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gordon YJ, Johnson B, Romanonski E, Araullo-Cruz T . RNA complementary to herpes simplex virus type 1 ICP0 gene demonstrated in neurons of human trigeminal ganglia. J Virol 1988; 62: 1832–1835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Thompson RL, Sawtell NM . The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. J Virol 1997; 71: 5432–5440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Thompson RL, Sawtell NM . Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival. J Virol 2001; 75: 6660–6675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Perng GC et al. A herpes simplex virus type 1 latency-associated transcript mutant with increased virulence and reduced spontaneous reactivation. J Virol 1999; 73: 920–929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Perng GC et al. The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits. J Virol 2000; 74: 1885–1891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Inman M et al. Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. J Virol 2001; 75: 3636–3646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Miranda-Saksena M et al. Anterograde transport of herpes simplex virus type 1 in cultured, dissociated human and rat dorsal root ganglion neurons. J Virol 2000; 74: 1827–1839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rivera L, Beuerman RW, Hill JM . Corneal nerves contain intra-axonal HSV-1 after virus reactivation by epinephrine iontophoresis. Curr Eye Res 1988; 7: 1001–1008.

    Article  CAS  PubMed  Google Scholar 

  118. Penfold ME, Armati P, Cunningham AL . Axonal transport of herpes simplex virions to epidermal cells: evidence for a specialized mode of virus transport and assembly. Proc Natl Acad Sci USA 1994; 91: 6529–6533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Heidemann SR, Landers JM, Hamborg MA . Polarity orientation of axonal microtubules. J Cell Biol 1981; 91: 661–665.

    Article  CAS  PubMed  Google Scholar 

  120. Roller RJ, Roizman B . The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits. J Virol 1992; 66: 3624–3632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Kamal A et al. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 2000; 28: 449–459.

    Article  CAS  PubMed  Google Scholar 

  122. Kamal A et al. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 2001; 414: 643–648.

    Article  CAS  PubMed  Google Scholar 

  123. Yamamura J et al. Long-term gene expression in the anterior horn motor neurons after intramuscular inoculation of a live herpes simplex virus vector. Gene Therapy 2000; 7: 934–941.

    Article  CAS  PubMed  Google Scholar 

  124. Lachmann RH, Efstathiou S . Utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system. J Virol 1997; 71: 3197–3207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Whitbeck JC et al. Localization of the gD-binding region of the human herpes simplex virus receptor, HveA. J Virol 2001; 75: 171–180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Whitbeck JC et al. Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, and a mediator of HSV entry. J Virol 1997; 71: 6083–6093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhou G, Ye GJ, Debinski W, Roizman B . Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci USA 2002; 99: 15124–15129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Argnani R, Boccafogli L, Marconi PC, Manservigi R . Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide. Gene Therapy 2004; 11: 1087–1098.

    Article  CAS  PubMed  Google Scholar 

  129. Grandi P et al. HSV-1 virions engineered for specific binding to cell surface receptors. Mol Ther 2004; 9: 419–427.

    Article  CAS  PubMed  Google Scholar 

  130. Goins WF et al. A novel latency-active promoter is contained within the herpes simplex virus type 1 UL flanking repeats. J Virol 1994; 68: 2239–2252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Goins WF et al. Herpes simplex virus type 1 vector-mediated expression of nerve growth factor protects dorsal root ganglion neurons from peroxide toxicity. J Virol 1999; 73: 519–532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Marshall KR et al. Long-term transgene expression in mice infected with a herpes simplex virus type 1 mutant severely impaired for immediate-early gene expression. J Virol 2000; 74: 956–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Palmer JA et al. Development and optimization of herpes simplex virus vectors for multiple long-term gene delivery to the peripheral nervous system. J Virol 2000; 74: 5604–5618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Loeser J, Butler S, Chapman C, Turk K . Bonica's Management of Pain. Lippincott: Philadelphia, 2001.

    Google Scholar 

  135. Wilson SP et al. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci USA 1999; 96: 3211–3216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Goss JR et al. Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther 2001; 8: 551–556.

    Article  CAS  PubMed  Google Scholar 

  137. Goss JR et al. Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann Neurol 2002; 52: 662–665.

    Article  CAS  PubMed  Google Scholar 

  138. Yoshimura N et al. Gene therapy of bladder pain with herpes simplex virus (HSV) vectors expressing preproenkephalin (PPE). Urology 2001; 57: 116.

    PubMed  Google Scholar 

  139. Hao S et al. HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain. Mol Ther 2003; 8: 367–375.

    Article  CAS  PubMed  Google Scholar 

  140. Liu J et al. Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. Mol Ther 2004; 10: 57–66.

    Article  CAS  PubMed  Google Scholar 

  141. Goins WF et al. Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction. J Urol 2001; 165: 1748–1754.

    Article  CAS  PubMed  Google Scholar 

  142. Sasaki K et al. Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes 2004; 53: 2723–2730.

    Article  CAS  PubMed  Google Scholar 

  143. Chattopadhyay M et al. In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3. Ann Neurol 2002; 51: 19–27.

    Article  CAS  PubMed  Google Scholar 

  144. Chattopadhyay M et al. Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy. Brain 2004; 127: 929–939.

    Article  PubMed  Google Scholar 

  145. Chiocca EA et al. Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants. N Biol 1990; 2: 739–746.

    CAS  Google Scholar 

  146. Huang Q et al. Introduction of a foreign gene (Escherichia coli lacZ) into rat neostriatal neurons using herpes simplex virus mutants: a light and electron microscopic study. Exp Neurol 1992; 115: 303–316.

    Article  CAS  PubMed  Google Scholar 

  147. Lilley CE et al. Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene delivery to the central nervous system in vivo. J Virol 2001; 75: 4343–4356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    A R Frampton Jr, W F Goins, K Nakano, E A Burton & J C Glorioso

  2. Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    E A Burton

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  1. A R Frampton Jr
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  2. W F Goins
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  4. E A Burton
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Frampton, A., Goins, W., Nakano, K. et al. HSV trafficking and development of gene therapy vectors with applications in the nervous system. Gene Ther 12, 891–901 (2005). https://doi.org/10.1038/sj.gt.3302545

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