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Molecular biology of herpes simplex virus type 1 latency in the nervous system

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Abstract

Herpes simplex virus (HSV) is one of the best studied examples of viral ability to remain latent in the human nervous system and to cause recurrent disease by reactivation. Intensive effort was directed in recent years to unveil the molecular viral mechanisms and the virus-host interactions associated with latent HSV infection. The discovery of the state of the latent viral DNA in nervous tissues and of the presence of latency-associated gene expression during latent infection, both differing from the situation during viral replication, provided important clues relevant to the pathogenesis of latent HSV infection. This review summarizes the current state of knowledge on the site of latent infection, the molecular phenomena of latency, and the mechanisms of the various stages of latency: acute infection, establishment and maintenance of latency, and reactivation. This information paved the way to recent trials aiming to use herpes viruses as vectors to deliver genes into the nervous system, an issue that is also addressed in this review.

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References

  • Abgharis S. Z. and Stulting R. D. (1988) Recovery of herpes simplex virus from ocular tissues of latently infected inbred mice.Invest. Ophthalmol. Visual. Sci. 29, 239–243.

    Google Scholar 

  • Ace C. I., McKee T. A., Ryan J. M., Cameron J. M., and Preston C. M. (1989) Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate early gene expression.J. Virol. 63, 2260–2269.

    PubMed  CAS  Google Scholar 

  • Ash R. J. (1986) Butyrate-induced reversal of herpes simplex virus restriction in neuroblastoma cells.Virology 155, 584–592.

    PubMed  CAS  Google Scholar 

  • Ball M. J. (1982) Limbic predilection in Alzheimer dementia: is reactivated herpesvirus involved?Can. J. Neurol. Sci. 9, 303–306.

    PubMed  CAS  Google Scholar 

  • Baringer J. R. and Swoveland P. (1973) Recovery of herpes simplex virus from human trigeminal ganglions.N. Eng. J. Med. 288, 648–650.

    CAS  Google Scholar 

  • Bastian R. O., Rabson A. S., Yee C. L., and Tralka T. S. (1972) Herpes virus huminis: isolation from human trigeminal ganglia.Science 178, 306–307.

    PubMed  CAS  Google Scholar 

  • Batchelor A. H. and O'Hare 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 

  • Bernstein D. and Kappes J. C. (1988) Enhanced in vitro reactivation of latent herpes simplex virus from neural and peripheral tissues with hexamethylene bisacetamide.Arch. Virol. 99, 57–65.

    PubMed  CAS  Google Scholar 

  • Block T. M., Spivack J. G., Steiner I., Deshmane S., McIntosh M. T., Lirette R. P., and Fraser N. W. (1990) A herpes simplex virus type 1 latency-associated transcript mutant reactivates with normal kinetics from latent infection.J. Virol. 64, 3417–3426.

    PubMed  CAS  Google Scholar 

  • Brennand J., Konecki D. S., and Caskey C. T. (1983) Expression of human and Chinese hamster hypoxanthine-guanine phosphribosyltransferase cDNA recombinants in cultured Lesch-Nyhan and Chinese hamster fibroblasts.J. Biol. Chem. 258, 946–951.

    Google Scholar 

  • Cabrera C. V., Wohlenberg C., Openshaw H., Rey-Mendez M., Puga A., and Notkins A. L. (1980) Herpes simplex virus DNA sequences in the CNS of latently infected mice.Nature 288, 288–290.

    PubMed  CAS  Google Scholar 

  • Campbell M. E. M., Palfreyman J. W., and Preston C. M. (1984) Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription.J. Mol. Biol. 180, 1–19.

    PubMed  CAS  Google Scholar 

  • Campbell P. K., Kulozik A. E., Woodilam J. P., and Jones R. W. (1990) Induction by HMBA and DMSO of genes introduced into mouse erythroleukemia and other cell lines by transient transfection.Genes Develop. 4, 1252–1266.

    PubMed  CAS  Google Scholar 

  • Cheung A. K. (1989) Detection of pseudorabies virus transcripts in trigeminal ganglia of latently infected swine.J. Virol. 63, 2908–2913.

    PubMed  CAS  Google Scholar 

  • Clements G. B, and Subak-Sharpe J. (1988) Herpes simplex virus type 2 establishes latency in the mouse foodpad.J. Gen. Virol. 89, 375–383.

    Google Scholar 

  • Clements G. B. and Stow N. D. (1989) A herpes simplex virus type 1 mutant containing a deletion within immediate early gene 1 is latency-competent in mice.J. Gen. Virol. 70, 2501–2506.

    PubMed  CAS  Google Scholar 

  • Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Lieb D. A., Board C. L., Schaffer P. A., Tyler K. L., and Knipe D. M. (1989) Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactiveProc. Natl. Acad. Sci. USA 86, 4736–4740.

    PubMed  CAS  Google Scholar 

  • Cook S. D. and Brown S. M. (1987) Herpes simplex virus type 1 latency in rabbit corneal cells in vitro: reactivation and recombination following intratypic superinfection of long term cultures.J. Gen. Virol. 68, 813–824.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Cook M. L., Bastone V. B., and Stevens J. G. (1974) Evidence that neurons harbor latent herpes simplex virus.Infect. Immun. 9, 946–951.

    PubMed  CAS  Google Scholar 

  • Croen K. D., Ostrove J. M., Dragovic L. J., Smialek J. E., and Straus S. E. (1987) Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene “anti-sense” transcription byin situ hybridization.N. Eng. J. Med. 317, 1427–1432.

    CAS  Google Scholar 

  • Croen K. D., Ostrove J. M., Dragovic L. J., and Straus S. E. (1988) Patterns of gene expression and sites of latency in human nerve ganglia are different for varicella-zoster and herpes simplex viruses.Proc. Natl. Acad. Sci. USA 85, 9773–9777.

    PubMed  CAS  Google Scholar 

  • Cushing H. (1905) Surgical aspects of major neuralgia of trigeminal nerve: reports of 20 cases of operation on the Gasserian ganglion with anatomic and physiologic notes on the consequences of removal.JAMA 44, 1002–1008.

    Google Scholar 

  • Deatly A. M., Spivack J. G., Lavi E., and Fraser N. W. (1987) RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice.Proc. Natl. Acad. Sci. USA 84, 3204–3208.

    PubMed  CAS  Google Scholar 

  • Deatly A. M., Spivack J. G., Lavi E., O'Boyle D. R., and Fraser N. W. (1988) Latent herpes simplex virus type 1 transcripts in peripheral and central nervous system tissue of mice map to similar regions of the viral genome.J. Virol. 62, 749–756.

    PubMed  CAS  Google Scholar 

  • Deshmane S. L. and Fraser N. W. (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure.J. Virol. 63, 943–947.

    PubMed  CAS  Google Scholar 

  • Devi-Rao G. B., Goodart S. A., Hecht L. M., Rochford R., Rice M. K., and Wagner E. K. (1991) Relationship between polyadenylated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts.J. Virol. 65, 2179–2190.

    PubMed  CAS  Google Scholar 

  • Dobson A. T., Sedarati F., Devi-Rao G., Flanagan W. M., Farrell M. J., Stevens J. G., Wagner E. K., and Feldman L. T. (1989) Identification of the latency-associated transcript promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus.J. Virol. 63, 3844–3851.

    PubMed  CAS  Google Scholar 

  • Dobson A. T., Margolis T. P., Sedarati F., Stevens J. G., and Feldman L. T. (1990) A latent, nonpathogenic HSV-1 derived vector stably expresses β-galactosidase in mouse neurons.Neuron 5, 353–360.

    PubMed  CAS  Google Scholar 

  • Doerig C., Pizer L. I., and Wilcox C. L. (1991a) An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1.J. Virol. 65, 2724–2727.

    PubMed  CAS  Google Scholar 

  • Doerig C., Pizer L. I., and Wilcox C. L. (1991b) Detection of the latency-associated transcript in neuronal cultures during the latent infection with herpes simplex virus type 1.Virology 183, 423–426.

    PubMed  CAS  Google Scholar 

  • Dressler G. R., Rock D. L., and Fraser N. W. (1987) Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo.J. Gen. Virol. 68, 1761–1765.

    PubMed  CAS  Google Scholar 

  • Efstathiou S., Kemp S., Darby G., and Minson A. C. (1989) The role of herpes simplex virus type 1 thymidine kinase in pathogenesis.J. Gen. Virol. 70, 869–879.

    PubMed  CAS  Google Scholar 

  • Efstathiou S., Minson A. C., Field H. J., Anderson J. R., and Wildy P. (1986) Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans.J. Virol. 57, 446–455.

    PubMed  CAS  Google Scholar 

  • Eglin R. P., Lehner T., and Subak-Sharpe J. H. (1982) Detection of RNA complementary to herpes simplex virus in mononuclear cells from patients with Behcet's syndrome and recurrent oral ulcers.Lancet 2, 1356–1361.

    PubMed  CAS  Google Scholar 

  • Farrell M. J., Dobson A. T., and Feldman L. T. (1991) Herpes simplex virus latency-associated transcript is a stable intron.Proc. Natl. Acad. Sci. USA 88, 790–794.

    PubMed  CAS  Google Scholar 

  • Fazil J., MacLean A. R., and Brown S. M. (1991) Sequence analysis of the herpes simplex virus type 1 strain 17 variants 1704, 1705, and 1706 with respect to their origin and effect on the latency-associated transcript sequence.J. Gen. Virol. 72, 2311–2315.

    Google Scholar 

  • Fraser N. W., Lawrence N. C., Wroblewska Z., Gilden D. H., and Koprowski H. (1981) Herpes simplex virus type 1 DNA in human brain tissue.Proc. Natl. Acad. Sci. USA 78, 6461–6465.

    PubMed  CAS  Google Scholar 

  • Fraser N. W., Muggeridge M. I., Mellerick D. M., and Rock D. L. (1984) Molecular biology of HSV-1 latency in a mouse model system, inHerpesvirus (Rapp F., ed.), Liss, New York, pp. 159–173.

    Google Scholar 

  • Fraser N. W., Spivack J. G., Wroblewska Z., Block T., Deshmane S. L., Valvi-Nagy T., Natarajan R., and Gesser R. M. (1991) A review of the molecular mechanism of HSV-1 latency.Curr. Eye Res. 10(Suppl), 1–14.

    PubMed  Google Scholar 

  • Fuller A. O. and Spear P. G. (1987) Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus prevent virion cell fusion at the cell surface.Proc. Natl. Acad. Sci. USA 84, 5454–5458.

    PubMed  CAS  Google Scholar 

  • Galloway D. A., Fenoglio C., and McDougall J. K. (1982) Limited transcription of the herpes simplex virus genome when latent in human sensory ganglia.J. Virol. 41, 686–691.

    PubMed  CAS  Google Scholar 

  • Galloway D. A., Fenoglio C., Shevchuk M., and McDougall J. K. (1978) Detection of herpes simplex RNA in human sensory ganglia.Virology 95, 265–268.

    Google Scholar 

  • Gominak S., Cros D., and Paydarfar D. (1990) Herpes simplex labialis and trigeminal neuropathy.Neurology 40, 151–152.

    PubMed  CAS  Google Scholar 

  • Goodpasture E. W. (1929) Herpetic infections with special reference to involvement of the nervous system.Medicine 8, 223–243.

    Google Scholar 

  • Gordon Y. J., Johnson B., Romanowski E., and Araullo-Cruz T. (1988) RNA complementary to herpes simplex virus type 1 ICPO gene demonstrated in neurons of human trigeminal ganglia.J. Virol. 62, 1832–1835.

    PubMed  CAS  Google Scholar 

  • Green M. T., Courtney R. J., and Dunkel E. C. (1981) Detection of an immediate early herpes simplex virus type 1 polypeptide in trigeminal ganglia of latently infected animals.Infect. Immun. 34, 987–992.

    PubMed  CAS  Google Scholar 

  • Harbour D. A., Hill T. J., and Blyth W. A. (1981) Recurrent herpes simplex in the mouse: inflammation in the skin and activation of virus in the ganglia following peripheral stimuli.J. Gen. Virol. 64, 1491–1498.

    Google Scholar 

  • Harris R. A. and Preston C. M. (1991) Establishment of latency in vitro by the herpes simplex virus type 1 mutant in 1814.J. Gen. Virol. 72, 907–913.

    PubMed  CAS  Google Scholar 

  • Hill T. J., Blyth W. A., and Harbour D. A. (1978) Trauma to the skin causes recurrence of herpes simplex in the mouse.J. Gen. Virol. 39, 21–28.

    PubMed  CAS  Google Scholar 

  • Hill, T. J., Field H. J., and Blyth W. A. (1975) Acute and recurrent infection with herpes simplex virus in the mouse; a model for studying latency and recurrent disease.J. Gen. Virol. 28, 341–353.

    PubMed  CAS  Google Scholar 

  • Hill J. M., Sedarati F., Javier R. T., Wagner E. K., and Stevens J. G. (1990) Herpes simplex virus latent phase transcription facilitates in vivo reactivation.Virology 174, 117–125.

    PubMed  CAS  Google Scholar 

  • Ho D. Y. and Mocarski E. S. (1989) Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.Proc. Natl. Acad. Sci. USA 86, 7596–7600.

    PubMed  CAS  Google Scholar 

  • Javier R. T., Stevens J. G., Dissette V. B., and Wagner E. K. (1988) A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state.Virology 166, 254–257.

    PubMed  CAS  Google Scholar 

  • Johnson R. T. (1982)Viral Infections of the Nervous System. Raven, New York, pp. 129–157.

    Google Scholar 

  • Kastrukoff L. F., Lau A. S., and Kim S. U. (1987) Multifocal CNS demyelination following peripheral inoculation with herpes simplex virus type 1.Ann. Neurol. 22, 52–59.

    PubMed  CAS  Google Scholar 

  • Kaye S. B., Patterson A., Risk J. M., McCarthy K., and Hart C. A. (1991) Evidence for herpes simplex viral latency in the human cornea.Br. J. Ophthalmol. 75, 195–200.

    PubMed  CAS  Google Scholar 

  • Kemp L. M., Dent C. L., and Latchman D. S. (1990) Octamer motif mediates transcriptional repression of HSV immediate early genes and octamer-containing cellular promoters in neuronal cells.Neuron 4, 215–222.

    PubMed  CAS  Google Scholar 

  • Kennedy P. G. E., Al-Saadi S. A., and Clements G. B. (1983) Reactivation of latent herpes simplex virus from dissociated identified dorsal root ganglion cells in culture.J. Gen. Virol. 64, 1629–1635.

    PubMed  Google Scholar 

  • Krause P. R., Croen K. D., Straus S. E,, and Ostrove J. M. (1988) Detection and preliminary characterization of herpes simplex virus type 1 transcripts in latently infected human trigeminal ganglia.J. Virol. 62, 4819–4823.

    PubMed  CAS  Google Scholar 

  • Kristensson K., Lycke E., Roytta M., Svennerholm, B., and Vahlne A. (1986) Neuritic transport of herpes simplex 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. 67, 2023–2028.

    PubMed  CAS  Google Scholar 

  • Kuehn M. R., Bradley A., Robertson E. J., and Evans M. J. (1987) A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.Nature 326, 295–298.

    PubMed  CAS  Google Scholar 

  • Kuypers H. G. J. M., and Ugolini G. (1990) Viruses as transneuronal tracers.TINS 13, 71–75.

    PubMed  CAS  Google Scholar 

  • Lesch M., and Nyhan W. L. (1964) A familial disorder of uric acid metabolism and central nervous system function.Am. J. Med. 36, 561–570.

    PubMed  CAS  Google Scholar 

  • Lieb D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., and Schaffer P. A. (1989a) Immediate-early gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency.J. Virol. 63, 759–768.

    Google Scholar 

  • Lieb D. A., Bogard C. L., Kosz-Vnenchak M., Hicks K. A., Coen D. M., Knipe D. M., and Schaffer P. A. (1989b) A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from latent state with reduced frequency.J. Virol. 63, 2893–2900.

    Google Scholar 

  • Lieb D. A., Nadeau K. C., Rundle S. A., and Schaffer P. A. (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.

    Google Scholar 

  • Longnecker R., Roizman B., and Meignier B. (1988) Herpes simplex viruses as vectors: properties of a prototype vaccine strain suitable for use as a vector, inViral Vectors (Gluzman Y. and Hughes S. H., eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, p. 68.

    Google Scholar 

  • Lycke E., Hamark B., Johansson M., Krotochwil A., Lycke J., and Svennerholm, B. (1988) Herpes simplex virus infection of the human sensory neuron. An electron microscopy study.Arch. Virol. 101, 87–104.

    PubMed  CAS  Google Scholar 

  • Lycke E., Kristensson K., Svennerholm, B., Vahlne A., and Ziegler R. (1984) Uptake and transport of herpes simplex virus in neurites of rat dorsal root ganglia cells in culture.J. Gen. Virol. 65, 55–64.

    PubMed  Google Scholar 

  • McFarlane M., Daksis J. I., and Preston C. M. (1992) Hexamethylene bisacetamide stimulates herpes simplex virus immediate early gene expression in the absence of trans-induction by Vmw65.J. Gen. Virol. 73, 285–292.

    PubMed  CAS  Google Scholar 

  • McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., and Taylor P. (1988) The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1.J. Gen. Virol. 69, 1531–1574.

    PubMed  CAS  Google Scholar 

  • McGeoch D. J., Dolan A., Donald S., and Brauer D. H. K. (1986) Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1.Nucleic Acids Res. 14, 1727–1745.

    PubMed  CAS  Google Scholar 

  • MacLean A. R. and Brown M. S. (1987) Deletion and duplication variants around the long repeats of herpes virus type 1 strain 17.J. Gen. Virol. 68, 3019–3031.

    PubMed  Google Scholar 

  • McLennan J. L. and Darby G. (1980) Herpes simplex virus latency; the cellular location of virus in dorsal root ganglia and the fate of the infected cell following virus activation.J. Gen. Virol. 51, 233–243.

    PubMed  CAS  Google Scholar 

  • Mellerick D. M. and Fraser N. W. (1987) Physical state of the latent herpes simplex virus genome in mouse model system. Evidence suggesting an episomal state.Virology 158, 265–275.

    PubMed  CAS  Google Scholar 

  • Mitchell W. J., Lirette R. P., and Fraser N. W. (1990a) Mapping of low abundance latency-associated RNA in the trigeminal ganglia of mice latently infected with herpes simplex virus type 1.J. Gen. Virol. 71, 125–132.

    PubMed  CAS  Google Scholar 

  • Mitchell W. J., Steiner I., Brown S. M., MacLean A. R., Subak-Sharpe J. H., and Fraser N. W. (1990b) A herpes simplex virus type variant, deleted in the promoter region of the latency-associated transcripts, does not produce any detectable minor RNA species during latency in the mouse triggeminal ganglia.J. Gen. Virol. 71, 953–957.

    PubMed  CAS  Google Scholar 

  • Mitchell W. J., Deshmane S. L., Dolan A., McGeoch D. J., and Fraser N. W. (1990c) Characterization of herpes simplex virus type 2 transcription during latent infection of mouse trigeminal ganglia.J. Virol. 64, 5342–5348.

    PubMed  CAS  Google Scholar 

  • Mount S. M. (1982) A catalogue of splice junction sequences.Nucleic Acids Res. 10, 459–472.

    PubMed  CAS  Google Scholar 

  • Nesburn A. B., Elliot J. M., and Leibowitz H. M. (1967) Spontaneous reactivation of experimental herpes simplex keratitis in rabbits.Arch. Ophthalmol. 78, 523–529.

    PubMed  CAS  Google Scholar 

  • O'Hare P. and Goding C. R. (1988) Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation.Cell 52, 435–445.

    PubMed  Google Scholar 

  • Palella T. D., Silverman L. J., Schroll C. T., Homa F. L., Levine M., and Kelley W. N. (1988) Herpes simplex virus-mediated human hypoxanthineguanine phosphribosyltransferase gene transfer into neuronal cells.Mol. Cell. Biol. 8, 457–460.

    PubMed  CAS  Google Scholar 

  • Palella T. D., Hidaka Y., Silverman L. J., Levine M., Glorioso J., and Kelley W. N. (1989) Expression of human mRNA in brains of mice infected with a recombinant herpes simplex virus vector.Gene 80, 137–144.

    PubMed  CAS  Google Scholar 

  • Perry L. J. and McGeoch D. J. (1988) The DNA sequences of the long repeat regions and adjoining parts of the long unique region in the genome of herpes simplex virus type 1.J. Gen. Virol. 69, 2831–2846.

    PubMed  CAS  Google Scholar 

  • Plummer G. (1973) Isolation of herpes viruses from the trigeminal ganglia of man, monkeys and cats.J. Infect. Dis. 128, 345–348.

    PubMed  CAS  Google Scholar 

  • Poffenberger K. L. and Roizman B. (1985) Studies on a noninverting genome of a viable herpes simplex virus type 1. Presence of head to tail linkages of packaged genomes and requirements for circularization of infection.J. Virol. 53, 589–595.

    Google Scholar 

  • Post L. E., Mackem S., and Roizman B (1981) Regulation of a genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with a gene promoters.Cell 24, 555–565.

    PubMed  CAS  Google Scholar 

  • Preston C. M., Frame M. C., and Cambell M. E. M. (1988) A complex formed between cell components and a herpes simplex virus structural polypeptide binds to a viral immediate early gene regulatory region.Cell 52, 425–434.

    PubMed  CAS  Google Scholar 

  • Preston C. M., and Russell J. (1991) Retention of non-linear viral DNA during herpes simplex virus latency in vitro.Intervirology 32, 69–75.

    PubMed  CAS  Google Scholar 

  • Price R. W., Katz B. J., and Notkins A. L. (1975) Latent infection of the peripheral ANS with herpes simplex virus.Nature 257, 686–688.

    PubMed  CAS  Google Scholar 

  • Puga A., Rosenthal J. D., Openshaw, H., and Notkins A. L. (1978) Herpes simplex virus DNA and mRNA sequences in acutely and chronically infected trigeminal ganglia of mice.Virology 89, 102–111.

    PubMed  CAS  Google Scholar 

  • Read G. S. and Frenkel N. (1983) Herpes simplex virus mutants defective in the virion associated shut off of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (immediate early) viral polypeptides.J. Virol. 46, 498–512.

    PubMed  CAS  Google Scholar 

  • Rock D. L. and Fraser N. W. (1983) Detection of HSV-1 genome in the central nervous system of latently infected mice.Nature 302, 523–525.

    PubMed  CAS  Google Scholar 

  • Rock D. L. and Fraser N. W. (1985) Latent herpes simplex virus type 1 DNA contains two copies of the virion DNA joint region.J. Virol. 55, 849–852.

    PubMed  CAS  Google Scholar 

  • Rock D. L., Hagemoser W. A., Osorio F. A., and Reed D. E. (1986) Detection of bovine herpesvirus type 1 RNA in trigeminal ganglia of latently infected rabbits byin situ hybridization.J. Gen. Virol. 67, 2515–2520.

    PubMed  CAS  Google Scholar 

  • Rock D. L., Nesburn A. B., Ghiasi H., Ong J., Lewis T. L., Lokensgard J. R., and Wechsler S. L. (1987) Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1.J. Virol. 61, 3820–3826.

    PubMed  CAS  Google Scholar 

  • Rodda S., Jack I., and White D. O. (1973) Herpes simplex virus from the trigeminal ganglion.Lancet 1, 1395–1396.

    PubMed  CAS  Google Scholar 

  • Roizman B. and Jenkins F. J. (1985) Genetic engineering of novel genomes of large DNA viruses.Science 229, 1208–1214.

    PubMed  CAS  Google Scholar 

  • Roizman B. and Sears A. E. (1990) Herpes Simplex viruses and their replication, inVirology, 2nd Ed.,65 (Fields B. N., Knipe D. M. et al., eds.), Raven, New York, pp. 1795–1841.

    Google Scholar 

  • Roizman B. and Sears A. E. (1987) An inquiry into the mechanisms of herpes simplex virus latency.Ann. Rev. Microbiol. 41, 543–571.

    CAS  Google Scholar 

  • Russell J. and Preston C. M. (1986) An in vitro latency system for herpes simplex virus type 2.J. Gen. Virol. 67, 397–403.

    PubMed  Google Scholar 

  • Russell J., Stow N. D., Stow E. C., and Preston C. M. (1987) Herpes simplex virus genes involved in latency in vitro.J. Gen. Virol. 68, 3009–3018.

    PubMed  Google Scholar 

  • Sawetell N. M. and Thompson R. L. (1992) Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency.J. Virol. 66, 2157–2169.

    Google Scholar 

  • Sears A. E., Halliburton I. W., Meignier B., Silver S., and Roizman B. (1985) Herpes simplex virus mutant deleted in the α22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice.J. Virol. 55, 338–346.

    PubMed  CAS  Google Scholar 

  • Sedarati F., Izumi K. M., Wagner E. K., and Stevens J. G. (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 

  • Shimomura Y., Gangarosa L. P., Kataoka M., and Hill J. M. (1983) HSV-1 shedding by iontophoresis of 6-hydroxydopamine followed by topical epinerphrine.Invest. Ophthalmol. Vis. Sci. 24, 1588–1594.

    PubMed  CAS  Google Scholar 

  • Spivack J. G. and Fraser N. W. (1987) Detection of herpes simplex type 1 transcripts during latent infection in mice.J. Virol. 61, 3841–3847.

    PubMed  CAS  Google Scholar 

  • Spivack J. G. and Fraser N. W. (1988a) Expression of herpes simplex virus type 1 latency-associated transcripts in the trigeminal ganglia of mice during acute infection and reactivation of latent infection.J. Virol. 62, 1479–1485.

    PubMed  CAS  Google Scholar 

  • Spivack J. G. and Fraser N. W. (1988b) Expression of herpes simplex type 1 (HSV-1) latency-associated transcripts and transcripts affected by the deletion in avirulent mutant HFEM: Evidence for a new class of HSV-1 genes.J. Virol. 62, 3281–3287.

    PubMed  CAS  Google Scholar 

  • Spivack J. G., Woods G. M., and Fraser N. W. (1991) Identification of a novel latency-specific splice donor signal within the herpes simplex virus type 12.0-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., Spivack J. G., O'Boyle D. R., Lavi E., and Fraser N. W. (1988) Latent herpes virus type 1 transcription in human trigeminal ganglia.J. Virol. 62, 3493–3496.

    PubMed  CAS  Google Scholar 

  • Steiner I., Spivack J. G., Lirette R. P., Brown S. M., MacLean A. R., Subak-Sharpe J., and Fraser N. W. (1989) Herpes simplex virus type 1 latency-associated transcripts are evidently not essntial for latent infection.EMBO 8, 505–511.

    CAS  Google Scholar 

  • Steiner I., Spivack J. G., Deshmane S. L., Ace C. I., Preston C. M., and Fraser N. W. (1990) A herpes simplex virus type 1 mutant containing a non-transinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia.J. Virol. 64, 1630–1638.

    PubMed  CAS  Google Scholar 

  • Steiner I. and Kennedy P. G. E. (1991) Herpes simplex virus latency in the nervous system—a new model.Neuropathol. Appl. Neurobiol. 17, 433–440.

    PubMed  CAS  Google Scholar 

  • Stevens J. G. and Cook M. L. (1971) Latent herpes simplex virus in spinal ganglia of mice.Science 173, 843–845.

    PubMed  CAS  Google Scholar 

  • Stevens J. G., Nesburn A. B., and Cook M. L. (1972) Latent herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection.Nature New Biol. 235, 216–217.

    PubMed  CAS  Google Scholar 

  • Stevens J. G. (1978) Latent characteristics of selected herpesviruses.Adv. Cancer Res. 26, 227–256.

    PubMed  CAS  Google Scholar 

  • Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., and Feldman L. T. (1987) RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons.Science 235, 1056–1059.

    PubMed  CAS  Google Scholar 

  • Stevens J. G., Haarr L., Porter D. D., Cook M. L., and Wagner E. K. (1988) Prominence of the herpes simplex virus latency-associated transcript in trigeminal ganglia from seropositive humans.J. Infect. Dis. 158, 117–122.

    PubMed  CAS  Google Scholar 

  • Stevens J. G. (1989) Human herpesviruses: a consideration of the latent state.Microb. Rev. 53, 318–322.

    CAS  Google Scholar 

  • Stroop W. G., Rock D. L., and Fraser N. W. (1984) Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections byin situ hybridization.Lab. Invest. 51, 27–38.

    PubMed  CAS  Google Scholar 

  • Trousdale M. D., Steiner I., Spivack J. G., Deshmane S. L., Brown S. M., MacLean A. R., Subak-Sharp J. H., and Fraser N. W. (1991) In vivo and in vitro reactivation impairment of a herpes simplex virus type 1 latency-associated transcript variant in a rabbit eye model. J. Virol.65, 6989–6993.

    PubMed  CAS  Google Scholar 

  • Valyi-Nagy T., Deshmane S. L., Spivack J. G., Steiner I., Ace C. I., Preston C. M., and Fraser N. W. (1991a) Investigation of herpes simplex virus type 1 (HSV-1) gene expression and DNA synthesis during the establishment of latent infection by an HSV-1 mutant, in 1814, that does not replicate in mouse trigeminal ganglia.J. Gen. Virol. 72, 641–649.

    PubMed  CAS  Google Scholar 

  • Valyi-Nagy T., Deshmane S., Dillner A., and Fraser N. W. (1991b) Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus type 1 infection, and explantation of trigeminal ganglia.J. Virol. 65, 4142–4152.

    PubMed  CAS  Google Scholar 

  • Wagner E. K., Devi-Rao G., Feldman L. T., Dobson A. T., Zhang Y.-F., Flanagan W. M., and stevens J. G. (1988a) Physical characterization of the herpes simplex virus latency-associated transcripts in neurons.J. Virol. 62, 1194–1202.

    PubMed  CAS  Google Scholar 

  • Wagner E. K., Flanagan W. M., Devi-Rao G., Zhang Y.-F., Hill J. M., Anderson K. P., and Stevens J. G. (1988b) The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection.J. Virol. 62, 4577–4585.

    PubMed  CAS  Google Scholar 

  • Walz M. A., Yamamoto H., and Notkins A. (1976) Immunological response restricts number of cells in sensory gangli infected with herpes simplex virus.Nature 264, 554–559.

    PubMed  CAS  Google Scholar 

  • Wechsler S. L., Nesburn A. B., Watson R., Slanina S. M., and Ghiasi H. (1988) Fine mapping of the latency-related gene of herpes simplex virus type 1: alternate splicing produces distinct latency-related RNAs containing open reading frames.J. Virol. 62, 4051–4058.

    PubMed  CAS  Google Scholar 

  • Wechsler S. L., Nesburn A. B., Watson R., Zwaagstra J., and Ghiasi H. (1989) Sequence of the latency-related gene of herpes simplex virus type 1.Virology 168, 168–172.

    PubMed  CAS  Google Scholar 

  • Wheatley S. C., Dent C. L., Wood J. N., and Latchman D. S. (1991) A cellular factor binding to the TAATGARAT DNA sequence prevents the expression of the HSV immediate-early genes following infection of nonpermissive cell lines derived from dorsal root ganglion neurons.Exp. Cell Res. 194, 78–82.

    PubMed  CAS  Google Scholar 

  • Whitby A. J., Blyth W. A., and Hill T. J. (1987) The effect of DNA hypomethylation agents on the reactivation of herpes simplex virus from latently infected mouse ganglia in vitro.Arch. Virol. 97, 137–144.

    PubMed  CAS  Google Scholar 

  • Whitley R. J. (1985) Epidemiology of herpes simplex viruses, inThe Herpesviruses, vol. 3 (Roizman B., ed.), Plenum, New York, pp. 1–44.

    Google Scholar 

  • Whitley R. J. (1990) Herpes simplex viruses, inVirology 66, 2nd Ed. (Fields B. N., Knipe D. M. et al., eds.), Raven, New York, pp. 1843–1886.

    Google Scholar 

  • Whitley R., Lakeman A. D., Nahmias A., and Roizman B. (1982) DNA restriction-enzyme analysis of herpes simplex virus isolates obtained from patients with encephalitis.N. Eng. J. Med. 307, 1060–1062.

    CAS  Google Scholar 

  • Wigdahl B. L., Scheck A. C., de Clerq E., and Rapp F. (1982) High efficiency latency and reactivation of herpes simplex virus in human cells.Science 217, 1145–1146.

    PubMed  CAS  Google Scholar 

  • Wilcox C. L., Smith R. L., Freed C. R., and Johnson E. M. (1990) Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro.J. Neurosci.10, 1268–1275.

    PubMed  CAS  Google Scholar 

  • Wilcox C. L. and Johnson E. M. (1987) Nerve growth factor deprivation results in reactivation of latent herpes simplex virus in vitro.J. Virol. 61, 2311–2315.

    PubMed  CAS  Google Scholar 

  • Willey D. E., Trousdale M. D., and Nesburn A. B. (1984) Reactivation of murine latent HSV infection by epinephrine iontophoresis.Invest. Ophthalmol. Vis. Sci. 25, 945–950.

    PubMed  CAS  Google Scholar 

  • Wroblewska Z., Spivack J. G., Otte J., Steiner I., Brown M., MacLean A., and Fraser N. W. (1991) The HSV-1 latency associated transcript (LAT) variants 1704 and 1705 are glycoprotein C negative.Virus Res. 20, 193–200.

    PubMed  CAS  Google Scholar 

  • Yamamoto L. J., Tedder D. G., Ashley R., and Levin M. J. (1991) Herpes simplex virus type 1 in the cerebrospinal fluid of a patient with Mollaret's meningitis.N. Eng. J. Med. 325, 1082–1085.

    CAS  Google Scholar 

  • Yisraelli J. and Szyf M. (1984) Gene methylation pattern and expression, inDNA Methylation: Biochemistry and Biological Significance (RAzira A., Cedar H., and Riggs A. D., eds.), Springer-Verlag, New York, pp. 353–378.

    Google Scholar 

  • Youssoufian H., Hammer S. M., Hirsch M. S., and Mulder C. (1982) Methylation of the viral genome in an in vitro model of herpes simplex virus latency.Proc. Natl. Acad. Sci. USA 79, 2207–2210.

    PubMed  CAS  Google Scholar 

  • Zwaagstra J. C., Ghaisi H., Nesburn A. B., and Wechsler S. L. (1989) In vitro promoter activity associated with the latency-associated transcript gene of herpes simplex virus type 1.J. Gen. Virol. 70, 2163–2169.

    PubMed  CAS  Google Scholar 

  • Zwaagstra J. C., Ghaisi H., Slanina S. M., Nesburn A. B., Wheatley S. C., Lillycrop K., Wood J., Latchman D. S., Patel K., and Wechsler S. L. (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 transcript.J. Virol. 64, 5019–5028.

    PubMed  CAS  Google Scholar 

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  1. The Laboratory of Neurovirology, Department of Neurology, Hadassah University Hospital, Hebrew University-Hadassah Medical School, 91120, Jerusalem, Israel

    Israel Steiner

  2. The Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, G51 4TF, Glasgow, UK

    Peter G. E. Kennedy

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Steiner, I., Kennedy, P.G.E. Molecular biology of herpes simplex virus type 1 latency in the nervous system. Mol Neurobiol 7, 137–159 (1993). https://doi.org/10.1007/BF02935640

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