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Development of Herpes Simplex Virus as a Gene Transfer Vector for the Central Nervous System

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Part of the book series: Research and Perspectives in Neurosciences ((NEUROSCIENCE))

Abstract

Herpes simplex virus (HSV) is a large neurotropic virus containing 152 kb of linear dsDNA encoding at least 70 gene products. In natural human infections, the virus replicates primarily in skin or mucosal epithelial cells prior to entering regional axon terminals and retrograde transport of the virus capsid to sensory ganglia, where it may either replicate or establish latency (Roizman and Sears 1990; Fig. 1). Latent virus can be reactivated by a variety of stimuli followed by anterograde transport and productive secondary infection at or near the primary site. In animals models, infection of peripheral sensory ganglia and latency can be achieved through inoculation of the skin (Cook and Stevens 1973), cornea (Sciler and Schwab 1984) or the olfactory bulb after intranasal inoculation (Dobson et al. 1989). Focal infection of specific brain regions can be achieved by stereotactic injection of small volumes of virus into defined brain regions (McFarland et al. 1986; Bak et al. 1977).

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References

  • Anderson WF (1984) Prospects for human gene therapy. Science 226:401–409

    Article  PubMed  CAS  Google Scholar 

  • Bak IJ, Markham CH, Cook ML, Stevens JG (1977) Intraaxonal transport of herpes simplex virus in the rat central nervous system. Brain Res 136:415–429

    Article  PubMed  CAS  Google Scholar 

  • Batchelor AH, O’Hara P (1990) Regulation and cell type-specific activity of a promoter located upstream of the latency-associated transcript of herpes simplex virus type 1. J Virol 64:3269–3279

    PubMed  CAS  Google Scholar 

  • Cook ML, Stevens JG (1973) Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence for intra-axonal transport of infection. Infect. Immun 7:272–288

    PubMed  CAS  Google Scholar 

  • Chou J, Kern ER, Whitley RJ, Roizman B (1990) Mapping of herpex simplex virus-1 neurovirulence to γ134.5, a gene nonessential for growth in culture. Science 250:1262–1266

    Article  PubMed  CAS  Google Scholar 

  • Chrisp CE, Averill DR, Sunstrum JC, Levine M, Glorioso JC (1989) Characterization of encephalitis in adult mice induced by intracerebral inoculation of herpes simplex virus type 1 (KOS) and comparison with mutants showing decreased virulence. Lab Invest 60:822–830

    PubMed  CAS  Google Scholar 

  • Coen DM, Kosz-Vnenchak M, Jacobsen JG, Leib DA, Bogard CL, Schaffer PA, Tyler KL, Knipe DM (1989) Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci USA 86:4736–4740

    Article  PubMed  CAS  Google Scholar 

  • Deatly AM, Spivack JG, Lavi E, Fraser NW (1987) RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglion of latently infected mice. Proc Natl Acad Sci USA 84:3204–3208

    Article  PubMed  CAS  Google Scholar 

  • DeLuca NA, McCarthy AM, Schaffer PA (1985) Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol 56:558–570

    PubMed  CAS  Google Scholar 

  • Devi-Rao GB, Goodart SA, Hecht LM, Rochford R, Rice MK, Wagner EK (1991) Relationship between polyadenylated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts. J Virol 65:2179–2190

    PubMed  CAS  Google Scholar 

  • Dobson AT, Sedarati F, Devi-Rao G, Flanagan WM, Farrell MJ, Stevens JG, Wagner EK, Feldmann LT (1989) Identification of the latency-associated transcript promoter by expression of rabbit β-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus. J Virol 63:3844–3851

    PubMed  CAS  Google Scholar 

  • Fink DJ, Sternberg LR, Weber PC, Mata M, Goins WF, Glorioso JC (1992) In vivo expression of β-galactosidase in hippocampal neurons by HSV-mediated gene transfer. Human Gene Ther 3:11–20

    Article  CAS  Google Scholar 

  • Forss-Petter S, Danielson PE, Catsicas S, Battenberg E, Price J, Nerenberg M and Sutcliffe JG (1990) Transgenic mice expressing β-galactosidase in mature neurons under revisions specific enolase promoter control. Neuron 5:187–197

    Article  PubMed  CAS  Google Scholar 

  • Hill TJ (1985) Herpes simplex virus latency. In The Herpesviruses, B. Roizmann (ed), Plenum Press, New York, pp 175–240

    Chapter  Google Scholar 

  • Ho DY, Mocarski ES (1989) herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc Natl Acad Sci USA 86:7596–7600

    Article  PubMed  CAS  Google Scholar 

  • Johnson JG, Leib DA, Goldstein DJ, Bogard CL, Schaffer PA, Weller SK, Coen DM (1989) A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive acute and reactivatable latent infections of mice and for replication in mouse cells. Virol 173:276–283

    Article  Google Scholar 

  • Julien PJ, Tretjakoff I, Bendaet L, Peterson A (1987) Expression and assembly of a human neurofilament protein in transgenic mice provide a novel neuronal marking systems. Genes Dev 1:1085–1095

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Leib DA, Bogard CL, Kosz-Vnenchak M, Hicks KA, Coen DM, Knipe DM, Schaffer PA (1989) A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequences. J Virol 63:2893–2900

    PubMed  CAS  Google Scholar 

  • Leib DA, Coen DM, Boargd CL, Hicks KA, Yager DR, Knipe DM, Tyler KL, Schaffer PA (1989) Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. J Virol 63:759–768

    PubMed  CAS  Google Scholar 

  • Leib DA, Nadeau KC, Rundle SA, Schaffer PA (1991) The promoter of the latency-associated transcripts of herpes simplex virus type 1 contains a functional cAMP-response element: role of the latency-associated transcripts and cAMP in reactivation of viral latency. Proc Natl Acad Sci USA 88:48–52

    Article  PubMed  CAS  Google Scholar 

  • Leist TP, Sandri-Goldin RM, Stevens JG (1989) Latent infections in spinal ganglia with thymidine kinase-deficient herpes simplex virus. J Virol 63:4976–4978

    PubMed  CAS  Google Scholar 

  • Longnecker R, Roizman B (1987) Clustering of genes dispensible for growth in culture in the S component of the HSV-1 genome. Science 236:573–576

    Article  PubMed  CAS  Google Scholar 

  • McCarthy AM, McMahan L, Schaffer PA (1989) Herpes simplex virus type 1 ICP27 deletion mutants exhibit altered patterns of transcription and are DNA deficient. J Virol 63:18–27

    PubMed  CAS  Google Scholar 

  • McFarland DJ, Sikora E, Hotchin J (1986) The production of focal encephalitis in mice by stereotaxic inoculation of virus: anatomical and behavioral effects. J Neurol Sci 72:307–318

    Article  PubMed  CAS  Google Scholar 

  • Meignier B, Longnecker R, Mavromara-Nazos P, Sears AE, Roizman B (1988) Virulence of and establishment of latency by genetically engineered deletion mutants of herpes simplex virus 1. Virology 162:251–254

    Article  PubMed  CAS  Google Scholar 

  • Melton DW, McEwan C, KcKie AB, Reid AM (1986) Expression of the mouse HPRT gene: deletional analysis of the promoter region of an X-chromosome linked housekeeping gene. Cell 44:319–328

    Article  PubMed  CAS  Google Scholar 

  • Nelson J, Baracchini E, Gould S, Ghazal P, Stenberg R, Wiley C (1991) The human cytomegalovirus immediate early promoter targets expression to the brain, salivary gland, pancreas, intestine, and testes of transgenic mice. 16th International Herpesvirus Workshop, p 176

    Google Scholar 

  • Perry JL, Rixon FJ, Everett RD, Frame MC, McGeoch DJ (1986) Characterization of the IE110 gene of herpes simplex virus type 1. J Gen Virol 67:2365–2380

    Article  PubMed  CAS  Google Scholar 

  • Puga A, Notkins AL (1987) Continued expression of a poly (A)+ transcript of herpes simplex virus type 1 in trigeminal ganglia of latently infected mice. J Virol 61:1700–1703

    PubMed  CAS  Google Scholar 

  • Rock DL, Nesbern AB, Ghiasi H, Ong J, Lewis TL, Lokensgard JR, Wechsler S (1987) Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex type 1. J Virol 61:3820–3826

    PubMed  CAS  Google Scholar 

  • Roizman B, Sears AE (1990) Herpes simplex viruses and their replication. In Virology, Fields BN, Knipe DM, Chanock RM, Hirsch MS, Melnick JL, Monath TP (eds.) 2nd ed Raven Press, New York, pp 1795–1841

    Google Scholar 

  • Sacks WR, Schaffer PA (1987) Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICPO exhibit impaired growth in cell culture. J Virol 61:829–839

    PubMed  CAS  Google Scholar 

  • Sauer BM, Whealy M, Robbins A, Enquist L (1987) Site-specific insertion of DNA into a pseudorabies virus vector. Proc Natl Acad Sci USA 84:9108–9112

    Article  PubMed  CAS  Google Scholar 

  • Sears AE, Halliburton IW, Meigner B, Silver S, Roizman B (1985) Herpes simplex virus 1 mutant delted in the a 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency. J Virol 55:338–346

    PubMed  CAS  Google Scholar 

  • Sedarati F, Izumi KM, Wagner EK, Stevens JG (1989) Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons. J Virol 63:4455–4458

    PubMed  CAS  Google Scholar 

  • Sciler M, Schwab ME (1984) Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basilis in the rat. Brain Res 300:33–39

    Article  Google Scholar 

  • Spivak JG, Fraser NW (1987) Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J Virol 61:3841–3847

    Google Scholar 

  • Spivack JG, Woods GM, Fraser NW (1991) Identification of a novel latency-specific splice donor signal within the herpes simplex virus type 1 2.0-kilobase latency-associated transcript (LAT): translation inhibition of LAT open reading frames by the intron within the 2.0-kilobase LAT. J Virol 65:6800–6810

    PubMed  CAS  Google Scholar 

  • Steiner I, Spivak JG, Lirette RP, Brown SM, MacLean AR, Subak-Sharpe JH, Fraser NW (1989) Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infecton. EMBO J 8:505–511

    PubMed  CAS  Google Scholar 

  • Stevens JG (1989) Human herpesviruses: a consideration of the latent state. Microbiol Rev 53:318–332

    PubMed  CAS  Google Scholar 

  • Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT (1987) RNA Complementary to a herpes virus a gene mRNA is prominent in latently infected neurons. Science 235:1056–1059

    Article  PubMed  CAS  Google Scholar 

  • Stow ND, Stow EC (1986) Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate-early peptide Vmw110. J Gen Virol 67:2571–2585

    Article  PubMed  CAS  Google Scholar 

  • Sunstrum JC, Chrips CE, Averill DR, Levine M, Glorioso JC (1988) Pathogeniticy of glycoprotein C negative mutants of herpes simplex virus type 1 for the mouse central nervous system. Virus Res 11:17–32

    Article  PubMed  CAS  Google Scholar 

  • Wagner EK, Devi-Rao G, Feldmann LT, Dobson AT, Zhang Y-F, Flanagan WM, Stevens JG (1988) Physical characterization of the herpes simplex virus latency-associated transcript in neurons. J Virol 62:1194–1202

    PubMed  CAS  Google Scholar 

  • Weber PC, Levine M, Glorioso JC (1987) Rapid identification of nonessential genes of herpes simplex virus type 1 by Tn5 mutagenesis. Science 236:576–579

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Sirko DA, McKnight JLC (1991) Role of herpes simplex virus type 1 UL46 and UL47 in alpha TIF-mediated transcriptional induction: characterization of three deletion mutants. J Virol 65:829–841

    PubMed  CAS  Google Scholar 

  • Zwaagstra JC, Ghiasi H, Nesburn AB, Wechsler SL (1989) In vitro promoter activity associated with the latency-associated transcript gene of herpes simplex virus type 1. J Gen Virol 70:2163–2169

    Article  PubMed  CAS  Google Scholar 

  • Zwaagstra JC, Ghiasi H, Slanina SM, Nesburn AG, Wheathley SC, Lillycrop K, Wood J, Latchman DS, Patel K, Wechsler SL (1990) Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcripts. J Virol 64:5019–5028

    PubMed  CAS  Google Scholar 

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© 1992 Springer-Verlag Berlin Heidelberg

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Glorioso, J.C., Sternberg, L.R., Goins, W.F., Fink, D.J. (1992). Development of Herpes Simplex Virus as a Gene Transfer Vector for the Central Nervous System. In: Gage, F.H., Christen, Y. (eds) Gene Transfer and Therapy in the Nervous System. Research and Perspectives in Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84842-1_11

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  • DOI: https://doi.org/10.1007/978-3-642-84842-1_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84844-5

  • Online ISBN: 978-3-642-84842-1

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