1887

Abstract

Transient expression assays in PC12 cells showed that the cAMP response element (CRE) and the TATA box of the herpes simplex virus type 1 latency-associated transcripts (LATs) promoter are essential for basal expression. Recombinant viruses were generated containing site-specific mutations in these motifs. The abilities of these recombinants to replicate, express LATs and reactivate from latency were compared with wild-type and marker-rescued viruses in a murine ocular model. The acute replication of these TATA and CRE mutant viruses was at a level equivalent to their respective marker-rescued viruses. The reactivation of virus was unaffected by mutation in the TATA box as compared with wild-type or marker-rescued viruses. hybridization of TATA box mutant virus-infected ganglia, however, showed threefold fewer LAT-positive neurons than wild-type virus-infected ganglia, with consistently weaker hybridization signals. Thus, this TATA box is required for normal expression of the LATs but not for efficient reactivation. The LATs CRE mutant reactivated with slightly but reproducibly reduced frequency and delayed kinetics relative to marker-rescued virus. By hybridization, however, the percentage and intensity of LATs-positive neurons were found to be comparable for the CRE mutant- and wild-type virus-infected ganglia, suggesting that the CRE is dispensable for abundant LATs expression but that a reactivation function of the LATs may depend upon the presence of the CRE. Finally, using a modified assay for examining the timing of reactivation, we showed that the induction of viral reactivation by addition of exogenous cAMP can occur independently of the LATs.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-9-1859
1993-09-01
2022-01-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/9/JV0740091859.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-9-1859&mimeType=html&fmt=ahah

References

  1. Batchelor AH, 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.. Journal of Virology 64:3269–3279
    [Google Scholar]
  2. Batchelor AH, O’Hare P. 1992; Localization of cis-acting sequence requirements in the promoter of the latency-associated transcript of herpes simplex virus type 1 required for cell-type-specific activity.. Journal of Virology 66:3573–3582
    [Google Scholar]
  3. Block TM, Spivack JG, Steiner I, Deshmane S, Macintosh MT, Lirette RP, Fraser NW. 1990; A herpes simplex type 1 latency-associated transcript mutant reactivates with normal kinetics from latent infection.. Journal of Virology 64:3417–3426
    [Google Scholar]
  4. Block TM, Spivack JG, Steiner I, Deshmane S, Macintosh MT, Lirette RP, Fraser NW. 1993; An HSV LAT null mutant reactivates slowly from latent infection and makes small plaques on CV-1 monolayers. Virology 192:618–630
    [Google Scholar]
  5. Chou J, Kern ER, Whitley RJ, Roizman B. 1990; Mapping of herpes simplex virus-1 neurovirulence to y, 34.5, a gene nonessential for growth in culture.. Science 250:1262–1265
    [Google Scholar]
  6. Clements GB, Stow ND. 1989; A herpes simplex virus type 1 mutant containing a deletion within immediate early gene 1 is latency-competent in mice. Journal of General Virology 70:2501–2506
    [Google Scholar]
  7. Coen DM, Irmiere AF, Jacobson JG, Kerns KM. 1989; Low levels of herpes simplex virus thymidine-thymidylate kinase are not limiting for sensitivity to certain antiviral drugs or for latency in a mouse model. Virology 168:221–231
    [Google Scholar]
  8. Croen KD, Ostrove JD, Dragovic LJ, Smialek JE, Straus SE. 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]
  9. Croen KD, Ostrove JM, Dragovic LJ, Straus SE. 1988; Patterns of gene expression and sites of latency are different for varicella-zoster and herpes simplex viruses.. Proceedings of the National Academy of Sciences, U.S.A. 85:9773–9777
    [Google Scholar]
  10. Croen KD, Ostrove JM, Dragovic LJ, Straus SE. 1991; Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and cell culture.. Journal of Infectious Diseases 163:23–28
    [Google Scholar]
  11. de la Maza MS, Wells PA, Foster CS. 1989; Cyclic nucleotide modulation of herpes simplex virus latency and reactivation.. Investigative Ophthalmology and Visual Science 30:2154–2159
    [Google Scholar]
  12. DeLuca NA, Courtney MA, Schaffer PA. 1984; Temperature sensitive mutants in HSV-1 ICP4 permissive for early gene expression.. Journal of Virology 52:767–776
    [Google Scholar]
  13. Devi-Rao GB, Goodart SA, Hecht LM, Rochford R, Rice MK, Wagner EK. 1991; Relationship between polyadenyl-ated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts.. Journal of Virology 65:2179–2190
    [Google Scholar]
  14. Dobson AT, Sedarati F, Devi-Rao G, Flanagan MT, Farrell MJ, Stevens JG, Wagner EK, Feldman LT. 1989; Identification of the latency-associated promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus.. Journal of Virology 63:3844–3851
    [Google Scholar]
  15. Doerig C, Pizer LI, Wilcox CL. 1991; An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1.. Journal of Virology 65:2724–2727
    [Google Scholar]
  16. Everett RD. 1984; Transactivation of transcription by herpes virus product: requirement for two HSV-1 immediate-early polypeptides for maximum activity.. EMBO Journal 3:3135–3141
    [Google Scholar]
  17. Farrell MJ, Dobson AT, Feldman LT. 1991; Herpes simplex virus latency-associated transcript is a stable intron. Proceedings of the National Academy of Sciences, U.S.A. 8:790–794
    [Google Scholar]
  18. Fraser NW, Block TM, Spivack JG. 1992; The latency associated transcripts of herpes simplex virus: RNA in search of function.. Virology 191:1–8
    [Google Scholar]
  19. Gelman IH, Silverstein S. 1985; Identification of immediate-early genes from herpes simplex virus that transactivate the viral kinase gene.. Proceedings of the National Academy of Sciences, U.S.A. 82:5265–5269
    [Google Scholar]
  20. Gorman CM, Moffat LF, Howard BH. 1982; Recombinant genomes which express chloramphenicol acetyl transferase in mammalian cells.. Molecular and Cellular Biology 6:4305–4316
    [Google Scholar]
  21. Hill JM, Sedarati F, Javier RT, Wagner EK, Stevens JG. 1990; Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174:117–125
    [Google Scholar]
  22. Ho DY, Mocarski ES. 1989; Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.. Proceedings of the National Academy of Sciences, U.S.A. 86:7596–7600
    [Google Scholar]
  23. Izumi KM, McKelvey AM, Devi-Rao G, Wagner EK, Stevens JG. 1989; Molecular and biological characterization of a type 1 herpes simplex virus (HSV-1) specifically deleted for expression of the latency-associated transcript (LAT).. Microbial Pathogenesis 7:121–134
    [Google Scholar]
  24. Javier RT, Stevens JG, Dissette VB, Wagner EK. 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]
  25. Kennedy PGE, Lisak RP, Raff MC. 1980; Cell type-specific markers for human glial and neuronal cells in culture.. Laboratory Investigation 43:342–351
    [Google Scholar]
  26. Kunkel TA. 1985; Rapid and efficient site-specific mutagenesis without phenotypic selection.. Proceedings of the National Academy of Sciences, U.S.A. 81:488–492
    [Google Scholar]
  27. Leib DA, Bogard CL, Kosz-Vnenchak M, Hicks KA, Coen DM, Knife DM, Schaffer PA. 1989a; 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]
  28. Leib DA, Coen DM, Bogard CL, Hicks KA, Yager DR, Knife DM, Tyler KL, Schaffer PA. 1989b; Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency.. Journal of Virology 63:759–768
    [Google Scholar]
  29. 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 latency.. Proceedings of the National Academy of Sciences, U.S.A. 88:48–52
    [Google Scholar]
  30. McGeoch DJ, 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]
  31. Mitchell WJ, Lirette RP, Fraser NW. 1990; Mapping of low abundance latency-associated RNA in the trigeminal ganglia of mice latently infected with herpes simplex vims type 1.. Journal of General Virology 71:125–132
    [Google Scholar]
  32. O’Hare P, Hayward GS. 1985a; Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation.. Journal of Virology 56:723–733
    [Google Scholar]
  33. O’Hare P, Hayward GS. 1985b; Evidence for direct role for both 175K and 110K immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters.. Journal of Virology 53:751–760
    [Google Scholar]
  34. Preston CM. 1979; Abnormal properties of an immediate early polypeptide in cells infected with herpes simplex virus type 1 mutant tsK.. Journal of Virology 32:357–369
    [Google Scholar]
  35. Quinlan MP, Knife DM. 1985; Stimulation of expression of a herpes simplex virus DNA-binding protein by two viral functions.. Molecular and Cellular Biology 5:967–963
    [Google Scholar]
  36. Rock DL, Beam SL, Mayfield JE. 1987; Mapping bovine herpesvirus type 1 latency-related RNA in trigeminal ganglia of latently infected rabbits.. Journal of Virology 61:3827–3831
    [Google Scholar]
  37. Rock DL, Hagemoser WA, Osorio FA, McAllister HA. 1988; Transcription from the pseudorabies virus genome during latent infection.. Archives of Virology 98:99–106
    [Google Scholar]
  38. Sawtell NM, Thompson RL. 1992; Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency.. Journal of Virology 66:2157–2169
    [Google Scholar]
  39. Smith RL, Pizer LI, Johnson E. M, Wilcox CL. 1992; Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures.. Virology 188:311–318
    [Google Scholar]
  40. Southern EM. 1975; Detection of specific sequences among DNA fragments separated by gel electrophoresis.. Journal of Molecular Biology 98:503–517
    [Google Scholar]
  41. 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.. Journal of Virology 65:6800–6810
    [Google Scholar]
  42. Steiner L, Spivack 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 infection.. EMBO Journal 8:505–511
    [Google Scholar]
  43. Stevens JG, Wagner EK, Devi-Rao G, Cook ML, Feldman L. 1987; RNA complementary to herpesvirus a-gene mRNA is predominant in latently infected neurons.. Science 235:1056–1059
    [Google Scholar]
  44. Trousdale MD, Steiner L, Spivack JG, Deshmane SL, Brown SM, MacLean AR, Subak-Sharpe JH, Fraser NW. 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]
  45. Wagner EK, Devi-Rao G, Feldman LT, Dobson AT, Zhang Y, Flanagan WM, Stevens JG. 1988a; Physical characterization of the herpes simplex virus latency-associated transcript in neurons.. Journal of Virology 62:1194–1202
    [Google Scholar]
  46. Wagner EK, Flanagan WM, Devi-Rao G, Zhang YF, Hill JM, Anderson KP, Stevens JG. 1988b; The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection.. Journal of Virology 62:4577–4585
    [Google Scholar]
  47. Watson R, Clements JB. 1980; A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis.. Nature, London 285:329–330
    [Google Scholar]
  48. Wechsler SL, Nesburn AB, Watson R, Slanina S, Ghiasi H. 1988; Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames.. Journal of Virology 62:4051–4058
    [Google Scholar]
  49. Zwaagstra J, Ghiasi H, Nesburn AB, Wechsler SL. 1989; In vitro promoter activity associated with the latency-associated transcript gene of herpes simplex virus type 1.. Journal of General Virology 70:2163–2169
    [Google Scholar]
  50. Zwaagstra JC, Ghiasi H, Slanina SM, Nesburn AB, Wheatley 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 transcript.. Journal of Virology 64:5019–5028
    [Google Scholar]
  51. Zwaagstra J, Ghiasi H, Nesburn AB, Wechsler SL. 1991; Identification of a major regulatory sequence in the latency associated transcript (LAT) promoter of herpes simplex virus type 1 (HSV-1).. Virology 182:287–297
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-9-1859
Loading
/content/journal/jgv/10.1099/0022-1317-74-9-1859
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error