This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mador, N.
Right arrow Articles by Steiner, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mador, N.
Right arrow Articles by Steiner, I.

 Previous Article  |  Next Article 

J Virol, June 1998, p. 5067-5075, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus Type 1 Latency-Associated Transcripts Suppress Viral Replication and Reduce Immediate-Early Gene mRNA Levels in a Neuronal Cell Line

Nurith Mador,1 Daniel Goldenberg,1 Oren Cohen,1 Amos Panet,2 and Israel Steiner1,*

Laboratory of Neurovirology, Department of Neurology, Hadassah University Hospital,1 and Department of Virology, The Hebrew University-Hadassah Medical School,2 Jerusalem, Israel

Received 16 October 1997/Accepted 12 March 1998

During herpes simplex virus type 1 (HSV-1) latent infection in human dorsal root ganglia, limited viral transcription, which has been linked to HSV-1 reactivation ability, takes place. To study the involvement of this transcription in HSV-1 replication in neuronal cells and consequently in viral latency, we constructed stably transfected neuronal cell lines containing (i) the entire HSV-1 latency transcriptionally active DNA fragment, (ii) the same DNA sequence with deletions of the latency-associated transcript (LAT) promoters, or (iii) the DNA coding sequence of the LAT domain. Replication of HSV-1 or a LAT-negative mutant was markedly repressed in the LAT-expressing cells, a phenomenon mediated by the LATs. To study the mechanism responsible for this effect, we examined LAT influence upon expression of HSV-1 immediate-early (IE) genes ICP0, ICP4, and ICP27, by Northern blot analysis. Following infection of a LAT-expressing neuronal cell line with a LAT-negative mutant, the steady-state levels of all three IE mRNAs were reduced compared to those for control cells. Transient transfections into a neuronal cell line indicated that the LAT suppressive effect upon ICP0 mRNA was mediated directly and was not due to the LAT effect upon the ICP0 promoter. We therefore propose that the LATs may repress viral replication in neuronal cells by reducing IE gene mRNA levels and thus facilitate the establishment of HSV-1 latency in nervous tissue.

* Corresponding author. Mailing address: Department of Neurology, Hadassah University Hospital, P.O. Box 12 000, Jerusalem 91120, Israel. Phone: 972/2/6776941. Fax: 972/2/6437782. E-mail: isteiner{at}md2.huji.ac.il

J Virol, June 1998, p. 5067-5075, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bertke, A. S., Patel, A., Krause, P. R. (2007). Herpes Simplex Virus Latency-Associated Transcript Sequence Downstream of the Promoter Influences Type-Specific Reactivation and Viral Neurotropism. J. Virol. 81: 6605-6613 [Abstract] [Full Text]  
  • Braun, E., Zimmerman, T., Hur, T. B., Reinhartz, E., Fellig, Y., Panet, A., Steiner, I. (2006). Neurotropism of herpes simplex virus type 1 in brain organ cultures.. J. Gen. Virol. 87: 2827-2837 [Abstract] [Full Text]  
  • Maillet, S., Naas, T., Crepin, S., Roque-Afonso, A.-M., Lafay, F., Efstathiou, S., Labetoulle, M. (2006). Herpes Simplex Virus Type 1 Latently Infected Neurons Differentially Express Latency-Associated and ICP0 Transcripts.. J. Virol. 80: 9310-9321 [Abstract] [Full Text]  
  • Ng, A. K., Block, T. M., Aiamkitsumrit, B., Wang, M., Clementi, E., Wu, T.-T., Taylor, J. M., Su, Y.-H. (2004). Construction of a Herpes Simplex Virus Type 1 Mutant with Only a Three-Nucleotide Change in the Branchpoint Region of the Latency-Associated Transcript (LAT) and the Stability of Its Two-Kilobase LAT Intron. J. Virol. 78: 12097-12106 [Abstract] [Full Text]  
  • Mador, N., Braun, E., Haim, H., Ariel, I., Panet, A., Steiner, I. (2003). Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene. J. Virol. 77: 12421-12429 [Abstract] [Full Text]  
  • Burton, E. A., Hong, C.-S., Glorioso, J. C. (2003). The Stable 2.0-Kilobase Intron of the Herpes Simplex Virus Type 1 Latency-Associated Transcript Does Not Function as an Antisense Repressor of ICP0 in Nonneuronal Cells. J. Virol. 77: 3516-3530 [Abstract] [Full Text]  
  • Jones, C. (2003). Herpes Simplex Virus Type 1 and Bovine Herpesvirus 1 Latency. Clin. Microbiol. Rev. 16: 79-95 [Abstract] [Full Text]  
  • Geiser, V., Inman, M., Zhang, Y., Jones, C. (2002). The latency-related gene of bovine herpesvirus-1 can inhibit the ability of bICP0 to activate productive infection. J. Gen. Virol. 83: 2965-2971 [Abstract] [Full Text]  
  • Chen, S.-H., Lee, L. Y., Garber, D. A., Schaffer, P. A., Knipe, D. M., Coen, D. M. (2002). Neither LAT nor Open Reading Frame P Mutations Increase Expression of Spliced or Intron-Containing ICP0 Transcripts in Mouse Ganglia Latently Infected with Herpes Simplex Virus. J. Virol. 76: 4764-4772 [Abstract] [Full Text]  
  • Thomas, S. K., Lilley, C. E., Latchman, D. S., Coffin, R. S. (2002). A Protein Encoded by the Herpes Simplex Virus (HSV) Type 1 2-Kilobase Latency-Associated Transcript Is Phosphorylated, Localized to the Nucleus, and Overcomes the Repression of Expression from Exogenous Promoters When Inserted into the Quiescent HSV Genome. J. Virol. 76: 4056-4067 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Ahmed, M., Fraser, N. W. (2001). Herpes Simplex Virus Type 1 2-Kilobase Latency-Associated Transcript Intron Associates with Ribosomal Proteins and Splicing Factors. J. Virol. 75: 12070-12080 [Abstract] [Full Text]  
  • Perng, G.-C., Esmaili, D., Slanina, S. M., Yukht, A., Ghiasi, H., Osorio, N., Mott, K. R., Maguen, B., Jin, L., Nesburn, A. B., Wechsler, S. L. (2001). Three Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutants with Distinct and Asymmetric Effects on Virulence in Mice Compared with Rabbits. J. Virol. 75: 9018-9028 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Burton, E. A., Wechuck, J. B., Wendell, S. K., Goins, W. F., Fink, D. J., Glorioso, J. C. (2001). Multiple Applications For Replication-Defective Herpes Simplex Virus Vectors. Stem Cells 19: 358-377 [Abstract] [Full Text]  
  • Thompson, R. L., Sawtell, N. M. (2001). Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene Promotes Neuronal Survival. J. Virol. 75: 6660-6675 [Abstract] [Full Text]  
  • Perng, G., 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. (2000). Virus-Induced Neuronal Apoptosis Blocked by the Herpes Simplex Virus Latency-Associated Transcript. Science 287: 1500-1503 [Abstract] [Full Text]  
  • Preston, C. M. (2000). Repression of viral transcription during herpes simplex virus latency. J. Gen. Virol. 81: 1-19 [Full Text]  
  • Yang, L., Voytek, C. C., Margolis, T. P. (2000). Immunohistochemical Analysis of Primary Sensory Neurons Latently Infected with Herpes Simplex Virus Type 1. J. Virol. 74: 209-217 [Abstract] [Full Text]  
  • Marshall, K. R., Lachmann, R. H., Efstathiou, S., Rinaldi, A., Preston, C. M. (2000). Long-Term Transgene Expression in Mice Infected with a Herpes Simplex Virus Type 1 Mutant Severely Impaired for Immediate-Early Gene Expression. J. Virol. 74: 956-964 [Abstract] [Full Text]  
  • Thomas, S. K., Gough, G., Latchman, D. S., R. S. , , Coffin, (1999). Herpes Simplex Virus Latency-Associated Transcript Encodes a Protein Which Greatly Enhances Virus Growth, Can Compensate for Deficiencies in Immediate-Early Gene Expression, and Is Likely To Function during Reactivation from Virus Latency. J. Virol. 73: 6618-6625 [Abstract] [Full Text]  
  • Perng, G.-C., Slanina, S. M., Yukht, A., Drolet, B. S., Keleher, W. Jr., Ghiasi, H., Nesburn, A. B., Wechsler, S. L. (1999). A Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutant with Increased Virulence and Reduced Spontaneous Reactivation. J. Virol. 73: 920-929 [Abstract] [Full Text]  
  • Rotola, A., Ravaioli, T., Gonelli, A., Dewhurst, S., Cassai, E., Di Luca, D. (1998). U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture. Proc. Natl. Acad. Sci. USA 95: 13911-13916 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»