1887

Abstract

In tissue culture, rat pheochromocytoma (PC12) cells differentiated with nerve growth factor (NGF) cease division, extend neuritic processes and acquire many properties characteristic of neuronal cells. In previous work, we have shown that NGF-differentiated PC12 cells can survive infection with herpes simplex virus type 1 (HSV-1) and maintain the viral genome in a quiescent but reactivatable state. In this study, we report that uninfected NGF-differentiated PC12 cells uniformly and predictably detach from the culture flask substratum after approximately 7 weeks. Although uninfected cells were uniformly lost from the culture by 7 weeks, surprisingly HSV-1-infected cells survived beyond 10 weeks, the time limit of the study. The detachment of uninfected cells was not the result of cell death or apoptosis, as determined by viability assays performed on cells after detachment. Expression of the HSV-1 latency associated transcript (LAT) gene and virus replication was not necessary for the virus to suppress the ‘detachment’ phenomenon, since NGF-differentiated PC12 cells infected with either wild-type, DNA polymerase mutant or LAT null mutant virus survived in culture for similar lengths of time. Viral gene expression does appear to be necessary for the suppression, however, since cells infected with UV-inactivated virus were lost from culture with kinetics similar to those of uninfected cells. These findings indicate that viral gene synthesis mediates changes to the host NGF-differentiated PC12 cells, which results in prevention of detachment.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-7-1591
2002-07-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/7/0831591a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-7-1591&mimeType=html&fmt=ahah

References

  1. Ahmed B., Lock M., Miller C. G., Fraser N. W. 2002; Regions of the herpes simplex virus type 1 latency-associated transcript that protect cells from apoptosis in vitro and protect neuronal cells in vivo. Journal of Virology 76:717–729
    [Google Scholar]
  2. Bruni R., Roizman B. 1998; Herpes simplex virus 1 regulatory protein ICP22 interacts with a new cell cycle-regulated factor and accumulates in a cell cycle-dependent fashion in infected cells. Journal of Virology 72:8525–8531
    [Google Scholar]
  3. Chen S. H., Kramer M., Schaffer P. A., Coen D. M. 1997; A viral function represses accumulation of transcripts from productive cycle genes in mouse ganglia latently infected with herpes simplex virus. Journal of Virology 71:5878–5884
    [Google Scholar]
  4. Danaher R. J., Jacob R. J., Miller C. S. 2000; Establishment of a quiescent herpes simplex virus type 1 infection in neurally-differentiated PC12 cells. Journal of NeuroVirology 5:258–267
    [Google Scholar]
  5. Davido D. J., Lieb D., Schaffer P. A. 2002; The cyclin-dependent? kinase inhibitor Roscovitine inhibits the transactivating activity and alters the posttranslational modification of herpes simplex virus type 1 ICP0. Journal of Virology 76:1077–1088
    [Google Scholar]
  6. 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]
  7. Everett R. D., Maul G. G. 1994; HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO Journal 13:5062–5069
    [Google Scholar]
  8. Garber D. A., Schaffer P. A., Knipe D. M. 1997; A LAT associated function reduces productive cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1. Journal of Virology 71:5885–5893
    [Google Scholar]
  9. Greene L. A., Tischler A. S. 1976; Establishment of a nonadrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proceedings of the National Academy of Sciences, USA 73:2424–2428
    [Google Scholar]
  10. Hammarsten O., Yao X., Elias P. 1996; Inhibition of topoisomerase II by ICRF-193 prevents efficient replication of herpes simplex virus type 1. Journal of Virology 70:4523–4529
    [Google Scholar]
  11. Hill A., Jugovic P., York I., Russ G., Bennink J., Yewdell J., Ploegh H., Johnson D. 1995; Herpes simplex virus turns off the TAP to evade host immunity. Nature 375:411–415
    [Google Scholar]
  12. Hill J. M., Sedarati F., Javier R. T., Wagner E. K., Stevens J. G. 1990; Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174:117–125
    [Google Scholar]
  13. Hobbs W. E., DeLuca N. A. 2001; Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0. Journal of Virology 73:8245–8255
    [Google Scholar]
  14. Hobbs W. E., Brough D. E., Kovesdi I., DeLuca N. A. 2001; Efficient activation of viral genomes by levels of herpes simplex virus ICP0 insufficient to affect cellular gene expression or cell survival. Journal of Virology 75:3391–3403
    [Google Scholar]
  15. Hwang Y. T., Liu B.-Y., Coen D. M., Hwang C. B. C. 1997; Effects of mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene on enzyme activities, viral replication, and replication fidelity. Journal of Virology 71:7791–7798
    [Google Scholar]
  16. Inman M., Perng G.-C., Henderson G., Ghiasi H., Nesburn A. B., Wechsler S. L., Jones C. 2001; Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. Journal of Virology 75:3636–3646
    [Google Scholar]
  17. Jordan R., Schang L., Schaffer P. A. 1999; Transactivation of herpes simplex virus type 1 immediate-early gene expression by virion-associated factors is blocked by an inhibitor of cyclin-dependent protein kinases. Journal of Virology 73:8843–8847
    [Google Scholar]
  18. Lieb D. A., Nadeau K. C., Rundle S. A., 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. Proceedings of the National Academy of Sciences, USA 88:48–52
    [Google Scholar]
  19. Lomonte P., Everett R. D. 1999; Herpes simplex virus type 1 immediate-early protein Vmw110 inhibits progression of cell through mitosis and from G1 into S phase of the cell cycle. Journal of Virology 73:9456–9467
    [Google Scholar]
  20. McLauchlan J., Simpson S., Clements J. B. 1989; Herpes simplex virus induces a processing factor that stimulates poly(A) site usage. Cell 59:1093–1105
    [Google Scholar]
  21. Marcy A. I., Yager D. R., Coen D. M. 1990; Isolation and characterization of herpes simplex virus mutants containing engineered mutations at the DNA polymerase locus. Journal of Virology 64:2208–2216
    [Google Scholar]
  22. Milligan C. E., Barnes N. Y., Urioste A. S. 2000; Mechanisms of neuronal death during development – insights from chick motorneurons. In Vivo 14:61–82
    [Google Scholar]
  23. Morrison J. H., Hof P. 1997; Life and death of neurons in the aging brain. Science 278:412–419
    [Google Scholar]
  24. Mossman K. L., MacGregor J., Rozmus J. J., Goryachev A. B., Edwards A. M., Smiley J. R. 2001; Herpes simplex virus triggers and then disarms a host antiviral response. Journal of Virology 75:750–758
    [Google Scholar]
  25. Perng G.-C., Dunkel E. C., Geary P. A., Slanina S. M., Ghiasi H., Kaiwar R., Nesburn A. B., Wechsler S. L. 1994; The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency. Journal of Virology 68:8045–8055
    [Google Scholar]
  26. Perng G.-C., Jones C., Ciacci-Zanella J., Stone M., Henderson G., Yukht A., Slanina S. M., Hofman F. M., Ghiasi H., Nesburn A. B., Wechsler S. L. 2000a; Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287:1500–1502
    [Google Scholar]
  27. Perng G.-C., Slanina S. M., Yukht A., Ghiasi H., Nesburn A. B., Wechsler S. L. 2000b; The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits. Journal of Virology 74:1885–1891
    [Google Scholar]
  28. Phelan A., Carmo-Fonseca M., McLauchlan J., Lamond A. I., Clements J. B. 1993; A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution. Proceedings of the National Academy of Sciences, USA 90:9056–9060
    [Google Scholar]
  29. Rock D. L., Nesburn A. B., Ghiasi H., Ong J., Lewis T. L., Lokensgard J. R., Wechsler S. L. 1987; Detection of herpes simplex virus type 1 latency-associated transcript expression in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. Journal of Virology 61:3820–3826
    [Google Scholar]
  30. Roizman B., Sears A. E. 1996; Herpes simplex viruses and their replication. In Fundamental Virology pp 2231–2296 Edited by Fields B. N., Knipe D. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  31. Sandri-Goldin R. M., Hibbard M. K., Hardwicke M. A. 1995; The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing. Journal of Virology 69:6063–6076
    [Google Scholar]
  32. Sawtell N. M., Thompson R. L. 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]
  33. Schaffer P. A., Aron G. M., Bemyesh-Melnick M. 1973; Temperature sensitive mutants of HSV 1 isolation, complementation and partial characterization. Journal of Virology 52:57–71
    [Google Scholar]
  34. Singh J., Simmen K., Lopper M., Frueh K., Compton T. 2001; Modulation of cellular transcriptional activity by HCMV glycoprotein B. In 25th International Herpesvirus Workshop, Portland, Oregon. 2000 abstract 202
    [Google Scholar]
  35. Song B., Liu J. J., Yeh K.-C., Knipe D. M. 2000; Herpes simplex virus infection block events in the G1 phase of the cell cycle. Virology 367:326–334
    [Google Scholar]
  36. Steiner I., Spivack J. G., Lirette R. P., Brown S. M., Maclean A. R., Subak-Sharpe J. H., Fraser N. W. 1989; Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO Journal 8:505–511
    [Google Scholar]
  37. Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. 1987; RNA complementary to a herpes virus gene mRNA is prominent in latently infected neurons. Science 235:1056–1059
    [Google Scholar]
  38. Stingley S. W., Ramirez J. G., Simmen K., Sandri-Goldin R. M., Ghazal P., Wagner E. K. 2000; Global analysis of herpes simplex virus type 1 transcription using an oligonucleotide-based DNA microarray. Journal of Virology 74:9916–9927
    [Google Scholar]
  39. Su Y.-H., Meegalla R. L., Chowan R., Cubitt C., Oakes J. E., Lausch R. L., Fraser N. W., Block T. M. 1999; Human corneal cells and other fibroblasts can stimulate the appearance of herpes simplex virus from quiescently infected PC12 cells. Journal of Virology 73:4171–4180
    [Google Scholar]
  40. Su Y.-H., Moxley M., Kejariwal R., Mehta A., Fraser N. W., Block T. M. 2000; The HSV 1 genome in quiescently infected NGF differentiated PC12 cells cannot be stimulated by HSV superinfection. Journal of NeuroVirology 6:341–349
    [Google Scholar]
  41. Thomselli K., Hall D. E., Flier L. A., Gehlsen K. R., Turner D. C., Carbonetto S., Reichardt L. F. 1990; A neuronal cell line PC12 expresses two β1-class integrins – α1β1 and α3b1 – that recognize different outgrowth-promoting domains in laminin. Neuron 5:651–662
    [Google Scholar]
  42. 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 type 1 latency-associated transcript variant in a rabbit eye model. Journal of Virology 65:6989–6993
    [Google Scholar]
  43. Yurochko A. D., Hwang E., Rasmussen L., Keay S., Pereira L., Huang E. 1997; The human cytomegalovirus UL55 (gB) and UL75 (gH) glycoprotein ligands initiate the rapid activation of Sp1 and NF-κB during infection. Journal of Virology 71:5051–5059
    [Google Scholar]
  44. Zhu H., Cong J., Shenk T. 1997; Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs. Proceedings of the National Academy of Sciences, USA 94:13985–13990
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-7-1591
Loading
/content/journal/jgv/10.1099/0022-1317-83-7-1591
Loading

Data & Media loading...

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