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 Sawtell, N. M.
Right arrow Articles by Thompson, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sawtell, N. M.
Right arrow Articles by Thompson, R. L.

 Previous Article  |  Next Article 

Journal of Virology, July 2004, p. 7784-7794, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7784-7794.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Comparison of Herpes Simplex Virus Reactivation in Ganglia In Vivo and in Explants Demonstrates Quantitative and Qualitative Differences

N. M. Sawtell1* and R. L. Thompson2

Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039,1 Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267-05242

Received 23 December 2003/ Accepted 12 March 2004

The in vivo ganglionic environment directs the latent herpes simplex virus transcriptional program. Since stress-driven perturbations in sensory neurons are thought to play a critical role in the transition from latency to reactivation, a primary concern in the selection of a valid model of the molecular interactions leading to reactivation is the faithful recapitulation of these environments. In this study reactivation of latently infected ganglia excised and cultured in vitro (explanted) is compared to reactivation occurring in latently infected ganglia in vivo following hyperthermic stress. Three notable points emerged. (i) Neurons in explanted ganglia exhibited marked morphological changes within 2 to 3 h postexplant. DNA fragmentation in neuronal nuclei was detected at 3 h, and atypical expression of cell cycle- and stress-regulated proteins such as geminin, cdk2, cdk4, and cytochrome c became apparent at 2 to 48 h. These changes were associated with axotomy and explant and not with the initiation or progression of reactivation and were not observed in ganglia following in vivo hyperthermic stress. (ii) Despite these differences, during the first 22 h primary reactivation events were restricted to a very small number of neurons in vivo and in explanted ganglia. This suggests that at any given time only a few latently infected neurons are competent to reactivate or that the probability of reactivation occurring in any particular neuron is very low. Importantly, the marked changes detected in explanted ganglia were not correlated with increased reactivation, demonstrating that these changes were not associated with the reactivation process per se. (iii) Secondary spread of virus was evident in explanted ganglia within 36 h, an event not observed in vivo. We conclude that explant reactivation may provide an ancillary system for selected studies of the early events in reactivation. However, clear signs of neuronal degeneration within 2 to 3 h postexplant indicate that these ganglia are undergoing major physiological changes not associated with the reactivation process. This ongoing neurodegeneration could alter even the early virus-host interactions in reactivation, and thus caution in the extrapolation of results obtained in explants to the in vivo interactions initiating reactivation is warranted.

* Corresponding author. Mailing address: Division of Infectious Diseases, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Phone: (513) 636-7880. Fax: (513) 636-7655. E-mail: Sawtn0{at}CHMCC.org.

Journal of Virology, July 2004, p. 7784-7794, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7784-7794.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Clement, C., Bhattacharjee, P. S., Kaufman, H. E., Hill, J. M. (2009). Heat-Induced Reactivation of HSV-1 in Latent Mice: Upregulation in the TG of CD83 and Other Immune Response Genes and Their LAT-ICP0 Locus. IOVS 50: 2855-2861 [Abstract] [Full Text]  
  • Margolis, T. P., Elfman, F. L., Leib, D., Pakpour, N., Apakupakul, K., Imai, Y., Voytek, C. (2007). Spontaneous Reactivation of Herpes Simplex Virus Type 1 in Latently Infected Murine Sensory Ganglia. J. Virol. 81: 11069-11074 [Abstract] [Full Text]  
  • Thompson, R. L., Sawtell, N. M. (2006). Evidence that the Herpes Simplex Virus Type 1 ICP0 Protein Does Not Initiate Reactivation from Latency In Vivo. J. Virol. 80: 10919-10930 [Abstract] [Full Text]  
  • Sawtell, N. M., Thompson, R. L., Haas, R. L. (2006). Herpes Simplex Virus DNA Synthesis Is Not a Decisive Regulatory Event in the Initiation of Lytic Viral Protein Expression in Neurons In Vivo during Primary Infection or Reactivation from Latency. J. Virol. 80: 38-50 [Abstract] [Full Text]  
  • Pesola, J. M., Zhu, J., Knipe, D. M., Coen, D. M. (2005). Herpes Simplex Virus 1 Immediate-Early and Early Gene Expression during Reactivation from Latency under Conditions That Prevent Infectious Virus Production. J. Virol. 79: 14516-14525 [Abstract] [Full Text]  
  • Decman, V., Kinchington, P. R., Harvey, S. A. K., Hendricks, R. L. (2005). Gamma Interferon Can Block Herpes Simplex Virus Type 1 Reactivation from Latency, Even in the Presence of Late Gene Expression. J. Virol. 79: 10339-10347 [Abstract] [Full Text]  
  • Zerboni, L., Ku, C.-C., Jones, C. D., Zehnder, J. L., Arvin, A. M. (2005). Varicella-zoster virus infection of human dorsal root ganglia in vivo. Proc. Natl. Acad. Sci. USA 102: 6490-6495 [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»