1887

Abstract

The latency-associated transcript (LAT) promoter of pseudorabies virus (PRV) is unique among viral promoters in that it remains active in trigeminal ganglia during the latent state. It is not known which the viral or host proteins regulate expression of the PRV LAT gene in latently infected neurons. To determine whether host transcriptional proteins in neurons can regulate the PRV LAT promoter , three transgenic mouse lines containing the PRV LAT promoter (LAP; LAP1 and LAP2) linked to the chloramphenicol acetyltransferase (CAT) gene were generated. All of the transgenic mouse lines, in the absence of the viral proteins, displayed strong expression of the transgene in trigeminal ganglia in addition to other neuronal tissues such as cerebral cortex, cerebellum, hippocampus and olfactory bulb. Expression of the transgene in neurons of trigeminal ganglia was demonstrated by hybridization. These data provide direct evidence that neuronal transcription factors are sufficient to activate the PRV LAP and that the promoter is neuron-specific.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19080-0
2003-08-01
2020-01-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/8/vir842015.html?itemId=/content/journal/jgv/10.1099/vir.0.19080-0&mimeType=html&fmt=ahah

References

  1. Ahmed, M., 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. J Virol 76, 717–729.[CrossRef]
    [Google Scholar]
  2. Block, T. M., Deshmane, S., Masonis, J., Maggioncalda, J., Valyi-Nagi, T. & Fraser, N. W. ( 1993; ). An HSV LAT null mutant reactivates slowly from latent infection and makes small plaques on CV-1 monolayers. Virology 192, 618–630.[CrossRef]
    [Google Scholar]
  3. Bloom, D. C., Devi-Rao, G. B., Hill, J. M., Stevens, J. G. & Wagner, E. K. ( 1994; ). Molecular analysis of herpes simplex virus type 1 during epinephrine-induced reactivation of latently infected rabbits in vivo. J Virol 68, 1283–1292.
    [Google Scholar]
  4. Cheung, A. K. ( 1989a; ). Detection of pseudorabies virus transcripts in trigeminal ganglia of latently infected swine. J Virol 63, 2908–2913.
    [Google Scholar]
  5. Cheung, A. K. ( 1989b; ). DNA nucleotide sequence analysis of the immediate-early gene of pseudorabies virus. Nucleic Acids Res 17, 4637–4646.[CrossRef]
    [Google Scholar]
  6. Cheung, A. K. ( 1991; ). Cloning of the latency gene and the early protein 0 gene of pseudorabies virus. J Virol 65, 5260–5271.
    [Google Scholar]
  7. Cheung, A. K. & Smith, T. A. ( 1999; ). Analysis of the latency-associated transcript/UL1–3.5 gene cluster promoter complex of pseudorabies virus. Arch Virol 144, 381–391.[CrossRef]
    [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. J Virol 71, 5885–5893.
    [Google Scholar]
  9. Hammer, R. E., Krumlauf, R., Camper, S. A., Brinster, R. L. & Tilghman, S. L. ( 1987; ). Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science 235, 53–58.[CrossRef]
    [Google Scholar]
  10. Herdegen, T. & Leah, J. D. ( 1998; ). Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Rev 28, 370–490.[CrossRef]
    [Google Scholar]
  11. 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.[CrossRef]
    [Google Scholar]
  12. Huang, C. J., Rice, M. K., Devi-Rao, G. B. & Wagner, E. K. ( 1994; ). The activity of the pseudorabies virus latency-associated transcript promoter is dependent on its genomic location in herpes simplex virus recombinants as well as on the type of cell infected. J Virol 68, 1972–1976.
    [Google Scholar]
  13. 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. J Virol 75, 3636–3646.[CrossRef]
    [Google Scholar]
  14. Jin, L. & Scherba, G. ( 1999; ). Expression of the pseudorabies virus latency-associated transcript gene during productive infection of cultured cells. J Virol 73, 9781–9788.
    [Google Scholar]
  15. Koedood, M. A., Fichtel, A., Meier, P. & Mitchell, P. J. ( 1995; ). Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection. J Virol 69, 2194–2207.
    [Google Scholar]
  16. Kramer, M. F., Chen, S. H., Knipe, D. M. & Coen, D. M. ( 1998; ). Accumulation of viral transcripts and DNA during establishment of latency by herpes simplex virus. J Virol 72, 1177–1185.
    [Google Scholar]
  17. Krause, P. R., Stanberry, L. R., Bourne, N., Connelly, B., Kurawadwala, J. F., Patel, A. & Straus, S. E. ( 1995; ). Expression of the herpes simplex virus type 2 latency-associated transcript enhances spontaneous reactivation of genital herpes in latently infected guinea pigs. J Exp Med 181, 297–306.[CrossRef]
    [Google Scholar]
  18. Leib, D. A., Bogard, C. L., Kosz-Vnenchak, M., Hicks, K. A., Coen, D. M., Knipe, D. M. & Schaffer, P. A. ( 1989; ). A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. J Virol 63, 2893–2900.
    [Google Scholar]
  19. Loiacono, C. M., Myers, R. & Mitchell, W. J. ( 2002; ). Neurons differentially activate the herpes simplex virus type 1 immediate-early gene ICP0 and ICP27 promoters in transgenic mice. J Virol 76, 2449–2459.[CrossRef]
    [Google Scholar]
  20. Mitchell, W. J. ( 1995; ). Neurons differentially control expression of a herpes simplex virus type 1 immediate-early promoter in transgenic mice. J Virol 69, 7942–7950.
    [Google Scholar]
  21. Ono, E., Tasaki, T., Kobayashi, T. & 7 other authors ( 1999; ). Resistance to pseudorabies virus infection in transgenic mice expressing the chimeric transgene that represses the immediate-early gene transcription. Virology 262, 72–78.[CrossRef]
    [Google Scholar]
  22. Osorio, F. A. & Rock, D. L. ( 1992; ). A murine model of pseudorabies virus latency. Microb Pathog 12, 39–46.[CrossRef]
    [Google Scholar]
  23. 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. J Virol 68, 8045–8055.
    [Google Scholar]
  24. Perng, G. C., Jones, C., Ciacci-Zanella, J. & 8 other authors ( 2000; ). Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287, 1500–1503.[CrossRef]
    [Google Scholar]
  25. Priola, S. A. & Stevens, J. G. ( 1991; ). The 5′ and 3′ limits of transcription in the pseudorabies virus latency associated transcription unit. Virology 182, 852–856.[CrossRef]
    [Google Scholar]
  26. Roizman, B. ( 1990; ). Herpesviridae: a brief introduction. In Fields Virology, pp. 1787–1793. Edited by B. N. Fields & D. M. Knipe. New York: Raven Press.
  27. Rziha, H. J., Mettenleiter, T. C., Ohlinger, V. & Wittmann, G. ( 1986; ). Herpesvirus (pseudorabies virus) latency in swine: occurrence and physical state of viral DNA in neural tissues. Virology 155, 600–613.[CrossRef]
    [Google Scholar]
  28. 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. J Virol 66, 2157–2169.
    [Google Scholar]
  29. Taharaguchi, S., Kobayashi, T., Yoshino, S. & Ono, E. ( 2002; ). Analysis of regulatory functions for the region located upstream from the latency-associated transcript (LAT) promoter of pseudorabies virus in cultured cells. Vet Microbiol 85, 197–208.[CrossRef]
    [Google Scholar]
  30. Tanaka, S. & Mannen, K. ( 2002; ). Activation of latent pseudorabies virus infection in mice treated with acetylcholine. Exp Anim 51, 407–409.[CrossRef]
    [Google Scholar]
  31. Thompson, R. L. & Sawtell, N. M. ( 1997; ). The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. J Virol 71, 5432–5440.
    [Google Scholar]
  32. Thompson, R. L. & Sawtell, N. M. ( 2001; ). Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival. J Virol 75, 6660–6675.[CrossRef]
    [Google Scholar]
  33. Wang, K., Pesnicak, L., Guancial, E., Krause, P. R. & Straus, S. E. ( 2001; ). The 2·2-kilobase latency-associated transcript of herpes simplex virus type 2 does not modulate viral replication, reactivation, or establishment of latency in transgenic mice. J Virol 75, 8166–8172.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19080-0
Loading
/content/journal/jgv/10.1099/vir.0.19080-0
Loading

Data & Media loading...

Most cited articles

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