1887

Abstract

The herpes simplex virus type 1 (HSV-1) γ34.5 gene is located within a region that is transcriptionally active during latent HSV-1 infection. To determine whether the γ34.5 gene deletion affects latency-associated transcript (LAT) gene expression or latent HSV-1 infection, a γ34.5 gene deletion mutant, 1716, and a stop codon insertion mutant, 1771, were studied in the mouse eye model. Although the γ34.5 gene is not essential, 1716 and 1771 replicated poorly in mouse eyes and trigeminal ganglia (TG). When mice were inoculated with 1716, infectious virus was detected in eyes only on the first day post-infection (p.i.), and was not detected at any time point in TG. Following inoculation with 1771, a small amount of virus was detected in the eyes on days 2 and 4 p.i., and in the TG of one animal on day 2 p.i. Reactivation of virus from mice latently infected with 1716 (0/30 TG) and 1771 (1/20 TG) was extremely low compared with the parental strain, 17, and appropriate rescuants (80 to 100% reactivation), even though latent 1716 DNA was detected by PCR in 50% of TG. These results differ from those obtained following footpad inoculation; in the footpad there was limited 1716 replication and reactivatable latent infection was established in some dorsal root ganglia. The data support the hypothesis that the role of γ34.5 may be tissue and/or cell type specific. The synthesis, processing, and stability of the 2.0 kb LAT during 1716 and 1771 replication was not affected by these mutations in the γ34.5 gene. However, during latent infection of 1716 in mice the LATs were not detectable in TG by Northern blot, and were present in reduced amounts (≈ 10-fold less) during 1771 latency. The LATs from 1716 were barely detectable in a few neurons by hybridization. Therefore, the γ34.5 gene might (i) affect replication in the eye, and reduce the amount of virus available to establish latent infection, be directly involved in (ii) establishment of latency, and/or (iii) the reactivation process.

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1995-02-01
2021-10-17
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References

  1. Ackermann M., Chou J., Sarmiento M., Lerner R. A., Roizman B. 1986; Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome. Journal of Virology 58:843–850
    [Google Scholar]
  2. Block T. M., Spivack J. G., Steiner I., Deshmane S., Lirette R. P., McIntosh M., Fraser N. W. 1990; A herpes simplex virus type 1 latency-associated transcript mutant reactivates with normal kinetics from latent infection. Journal of Virology 64:3417–3426
    [Google Scholar]
  3. Bohenzky R. A., Papavassiliou A. G., Gelman I. H., Silverstein S. 1993; Identification of a promoter mapping within the reiterated sequences that flank the herpes simplex virus type 1 UL region. Journal of Virology 67:632–642
    [Google Scholar]
  4. Bolovan C. A., Sawtell N. M., Thompson R. L. 1994; ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. Journal of Virology 68:48–55
    [Google Scholar]
  5. Brown S. M., Harland J., MacLean A. R., Podlech J., Clements J. B. 1994; Cell type and cell state determine differential in vitro growth of non-neurovirulent ICP34.5-negative herpes simplex virus types 1 and 2. Journal of General Virology 75:2367–2377
    [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. 1979; Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
    [Google Scholar]
  7. Chou J., Roizman B. 1986; The terminal ‘a’ sequence of the herpes simplex virus genome contains the promoter of a gene located in the repeat sequence of the L component. Journal of Virology 57:629–637
    [Google Scholar]
  8. Chou J., Roizman B. 1990; The herpes simplex virus 1 gene for ICP34.5 which maps in inverted repeats is conserved in several limited passage isolates but not in strain 17 syn+ . Journal of Virology 64:1014–1020
    [Google Scholar]
  9. Chou J., Roizman B. 1992; The γ 134.5 gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proceedings of the National Academy of Sciences, USA 89:3266–3270
    [Google Scholar]
  10. Chou J., Kern E. R., Whitley R. J., Roizman B. 1990; Mapping of herpes simplex virus-1 neurovirulence to γ 134.5, a gene nonessential for growth in culture. Science 250:1262–1266
    [Google Scholar]
  11. Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Leib D. A., Bogard C. L., Schaffer P. A., Tyler K. L., Knipe D. M. 1989; Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proceedings of the National Academy of Sciences, USA 86:4736–4740
    [Google Scholar]
  12. Cook M. L., Bastone V. B., Stevens J. G. 1974; Evidence that neurons harbor latent herpes simplex virus. Infection and Immunity 9:946–951
    [Google Scholar]
  13. Croen K. D., Ostrove J. M., Dragovic L. J., Smialek J. E., Straus S. E. 1987; Latent herpes simplex virus in human trigeminal ganglia: detection of an immediate early gene ‘anti-sense’ transcript by in situ hybridization. New England Journal of Medicine 317:1427–1432
    [Google Scholar]
  14. Deatly A. M., Spivack J. G., Lavi E., Fraser N. W. 1987; RNA from an immediate early region of the HSV-1 genome is present in the trigeminal ganglia of latently infected mice. Proceedings of the National Academy of Sciences, USA 84:3204–3208
    [Google Scholar]
  15. Deatly A. M., Spivack J. G., Lavi E., O’Boyle D. R. II, Fraser N. W. 1988; Latent herpes simplex virus type 1 transcripts in peripheral and central nervous system tissues of mice map to similar regions of the viral genome. Journal of Virology 62:749–756
    [Google Scholar]
  16. Dolan A., McKie E., MacLean A. R., McGeoch D. J. 1992; Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17. Journal of General Virology 73:971–973
    [Google Scholar]
  17. Fareed M. U., Spivack J. G. 1994; Two open reading frames (ORF1 and ORF2) within the 20-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency. Journal of Virology 68:8071–8081
    [Google Scholar]
  18. Fraser N. W., Block T. M., Spivack J. G. 1992; The latency-associated transcripts of herpes simplex virus: RNA in search of function. Virology 191:1–8
    [Google Scholar]
  19. Gordon Y. J., Johnson B., Romanowski E., Araullo-Cruz T. 1988; RNA complementary to herpes simplex virus type 1 ICP0 gene demonstrated in neurons of human trigeminal ganglia. Journal of Virology 62:1832–1835
    [Google Scholar]
  20. Hill J. M., Sederati F., Javier R. T., Wagner E. K., Stevens J. G. 1990; Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174:17–125
    [Google Scholar]
  21. Javier R. T., Stevens J. G., Dissette V. B., 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
    [Google Scholar]
  22. Katz J. P., Bodin E. T., Coen D. M. 1990; Quantitative polymerase chain reaction analysis of herpes simplex virus DNA in ganglia of mice infected with replication-incompetent mutants. Journal of Virology 64:4288–4295
    [Google Scholar]
  23. Kosz-Vnenchak M., Jacobson J., Coen D. M., Knipe D. M. 1993; Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. Journal of Virology 67:5383–5393
    [Google Scholar]
  24. Krause P. R., Croen K. D., Straus S. E., Ostrove J. M. 1988; Detection and preliminary characterization of herpes simplex virus type 1 transcripts in latently infected human trigeminal ganglia. Journal of Virology 62:4819–4823
    [Google Scholar]
  25. Leib D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., Schaffer P. A. 1989a; Immediate-early gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. Journal of Virology 63:759–768
    [Google Scholar]
  26. Leib D. A., Bogard C. L., Kosz-Vnenchak M., Hicks K. A., Coen D. M., Knipe D. M., Schaffer P. A. 1989b; A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. Journal of Virology 63:2893–2900
    [Google Scholar]
  27. McGeoch D. J., Cunningham C., McIntyre G., Dolan A. 1991; 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. Journal of General Virology 72:3057–3075
    [Google Scholar]
  28. McKay E. M., McVey B., Marsden H. S., Brown S. M., MacLean A. R. 1993; The herpes simplex virus type 1 strain 17 open reading frame RL1 encodes a polypeptide of apparent Mr 37K equivalent to ICP34.5 of herpes simplex virus type 1 strain F. Journal of General Virology 74:2493–2497
    [Google Scholar]
  29. McKie E. A., Hope R. G., Brown S. M., MacLean A. R. 1994; Characterization of the herpes simplex virus type 1 strain 17+ neurovirulence gene RL1 and its expression in a bacterial system. Journal of General Virology 75:733–741
    [Google Scholar]
  30. MacLean A. R., Fareed M. U., Robertson L., Harland J., Brown S. M. 1991; Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. Journal of General Virology 72:631–639
    [Google Scholar]
  31. McLennan J. L., 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. Journal of General Virology 51:233–243
    [Google Scholar]
  32. Mangano M. F., Hodinka R., Spivack J. G. 1992; Detection of human cytomegalovirus by polymerase chain reaction. In Diagnosis of Human Viruses by Polymerase Chain Reaction (PCR) Technology pp 147–156 Edited by Darai G., Becker Y. Heidelberg: Springer Verlag;
    [Google Scholar]
  33. Maniatis T., Fritsch E. F., Sambrook J. 1982 Molecular Cloning: A Laboratory Manual New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  34. Markert J. M., Malick A., Coen D. M., Martuza R. L. 1993; Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir. Neurosurgery 32:597–603
    [Google Scholar]
  35. Mitchell W. J., Lirette R. P., 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. Journal of General Virology 71:125–132
    [Google Scholar]
  36. Mitchell W. J., Steiner I., Brown S. M., MacLean A. R., Subak-Sharpe J. H., Fraser N. W. 1990b; A herpes simplex virus type 1 variant, deleted in the promoter region of the latency-associated transcripts, does not produce any detectable minor RNA species during latency in the mouse trigeminal ganglion. Journal of General Virology 71:953–957
    [Google Scholar]
  37. Perry L. J., McGeoch D. J. 1988; 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. Journal of General Virology 69:2831–2846
    [Google Scholar]
  38. Post L. E., Conley A. J., Mocarski E. S., Roizman B. 1980; Cloning of reiterated and nonreiterated herpes simplex virus 1 sequences as Bamiil fragments. Proceedings of the National Academy of Sciences, USA 77:4201–1205
    [Google Scholar]
  39. Robertson L. M., MacLean A. R., Brown S. M. 1992; Peripheral replication and latency reactivation kinetics of the nonneurovirulent herpes simplex virus type 1 variant 1716. Journal of General Virology 73:967–970
    [Google Scholar]
  40. Rock D. L., Nesburn A. B., Ghiasi H., Ong J., Lewis T. L., Lokensgard J. R., Wechsler S. 1987; Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. Journal of Virology 61:3820–3826
    [Google Scholar]
  41. Spivack J. G., Fraser N. W. 1987; Detection of herpes simplex virus type 1 transcripts during latent infection in mice. Journal of Virology 61:3841–3847
    [Google Scholar]
  42. Spivack J. G., Fraser N. W. 1988; Expression of herpes simplex virus type 1 latency-associated transcripts in the trigemminal ganglia of mice during acute infection and reactivation of latent infection. Journal of Virology 62:1479–1485
    [Google Scholar]
  43. Spivack J. G., O’Boyle D. R. II, Fraser N. W. 1987; Novobiocin and coumermycin A, inhibit viral replication and the reactivation of herpes simplex type I from the trigeminal ganglia of latently infected mice. Journal of Virology 61:3288–3291
    [Google Scholar]
  44. Spivack J. G., Woods G. M., Fraser N. W. 1991; Identification of a novel latency-specific splicing 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. Journal of Virology 65:6800–6810
    [Google Scholar]
  45. Steiner I., Spivack J. G., O’Boyle D. R. II, Lavi E., Fraser N. W. 1988; Latent herpes simplex virus type 1 transcription in human trigeminal ganglia. Journal of Virology 62:3493–3496
    [Google Scholar]
  46. Steiner I., Spivack J. G., Lirrete R. P., Brown S. M., MacLean A. R., Subak-Sharpe J. H., Fraser N. W. 1989; Herpes simplex virus latency-associated transcripts are evidently not essential for latent infection. EM BO Journal 8:505–511
    [Google Scholar]
  47. Steiner I., Spivack J. G., Deshmane S. L., Ace C. I., Preston C. M., Fraser N. W. 1990; A herpes simplex virus type 1 mutant containing a non-transducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. Journal of Virology 64:1630–1638
    [Google Scholar]
  48. Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. 1987; RNA complementary to a herpesvirus a gene mRNA is prominent in latently infected neurons. Science 235:1056–1059
    [Google Scholar]
  49. Stevens J. G., Haarr L., Porter D. D., Cook M. L., Wagner E. K. 1988; Prominence of the herpes simplex virus latency-associated transcript in ganglia from seropositive humans. Journal of Infectious Diseases 158:117–123
    [Google Scholar]
  50. Stroop W. G., Rock D. L., 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 infection by in situ hybridization. Laboratory Investigation 51:27–38
    [Google Scholar]
  51. Taha M. Y., Clements G. B., Brown S. M. 1989a; A variant of herpes simplex virus type 2 strain HG52 with a 1.5 kb deletion in RL between 0 to 0.02 and 0.81 to 0.83 map units is non-neurovirulent for mice. Journal of General Virology 70:705–716
    [Google Scholar]
  52. Taha M. Y., Clements G. B., Brown S. M. 1989b; The herpes virus type 2 (HG52) variant JH2604 has a 1488 bp deletion which eliminates neurovirulence in mice. Journal of General Virology 70:3073–3078
    [Google Scholar]
  53. Trousdale M. D., Steiner I., Spivack J. G., Deshmane S. L., Brown S. M., MacLean A. R., Subak-Sharpe J. H., 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. Journal of Virology 65:6989–6993
    [Google Scholar]
  54. Valyi-Nagy T., Deshmane S. L., Spivack J. G., Steiner I., Ace C. I., Preston C. M., Fraser N. W. 1991; Investigation of herpes simplex virus type 1 (HSV-1) gene expression and DNA synthesis during the establishment of latent infection by an HSV-1 variant, in 1814, that does not replicate in mouse trigeminal ganglia. Journal of General Virology 72:641–649
    [Google Scholar]
  55. Valyi-Nagy T., Fareed M. U., O’Keefe J. S., Gesser R. M., MacLean A. R., Brown S. M., Spivack J. G., Fraser N. W. 1994; The herpes simplex virus type 1 strain 17+ γ 34.5 deletion mutant 1716 is avirulent in SCID mice. Journal of General Virology 75:2059–2063
    [Google Scholar]
  56. Wagner E. K., Devi-Rao G., Feldman L. T., Dobson A. T., Zhang Y.-F., Flanagan W. M., Stevens J. G. 1988; Physical characterization of the herpes simplex virus latency-associated transcripts in neurons. Journal of Virology 62:1194–1202
    [Google Scholar]
  57. Whitley R. J., Kern E. R., Chatterjee S., Chou J., Roizman B. 1993; Replication, establishment of latency, and induced reactivation of herpes simplex virus y 1 34.5 deletion mutants in rodent models. Journal of Clinical Investigation 91:2837–2843
    [Google Scholar]
  58. Yeh L., Schaffer P. A. 1993; A novel class of transcripts expressed with late kinetics in the absence of ICP4 spans the junction between the long and short segments of the herpes simplex virus type 1 genome. Journal of Virology 67:7373–7382
    [Google Scholar]
  59. Zwaagstra J. C., Ghiasi H., Slanina S. M., Nesburn A. B., Wheatley S. C., Lillycrop K., Wood J., Latchman D. S., Patel K., 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. Journal of Virology 64:5019–5028
    [Google Scholar]
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