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Journal of Virology, February 2006, p. 1497-1512, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1497-1512.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Cellular Localization Pattern of Varicella-Zoster Virus ORF29p Is Influenced by Proteasome-Mediated Degradation

Christina L. Stallings,1,2 Gregory J. Duigou,2 Anne A. Gershon,3 Michael D. Gershon,4 and Saul J. Silverstein1,2*

Integrated Program in Cellular, Molecular and Biophysical Studies,1 Departments of Microbiology,2 Pediatrics,3 Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, 701 W. 168th St., New York, New York 100324

Received 22 June 2005/ Accepted 11 November 2005

Varicella-zoster virus (VZV) open reading frame 29 (ORF29) encodes a single-stranded DNA binding protein. During lytic infection, ORF29p is localized primarily to infected-cell nuclei, whereas during latency it appears in the cytoplasm of infected neurons. Following reactivation, ORF29p accumulates in the nucleus. In this report, we analyze the cellular localization patterns of ORF29p during VZV infection and during autonomous expression. Our results demonstrate that ORF29p is excluded from the nucleus in a cell-type-specific manner and that its cellular localization pattern may be altered by subsequent expression of VZV ORF61p or herpes simplex virus type 1 ICP0. In these cases, ORF61p and ICP0 induce nuclear accumulation of ORF29p in cell lines where it normally remains cytoplasmic. One cellular system utilized by ICP0 to influence protein abundance is the proteasome degradation pathway. Inhibition of the 26S proteasome, but not heat shock treatment, resulted in accumulation of ORF29p in the nucleus, similar to the effect of ICP0 expression. Immunofluorescence microscopy and pulse-chase experiments reveal that stabilization of ORF29p correlates with its nuclear accumulation and is dependent on a functional nuclear localization signal. ORF29p nuclear translocation in cultured enteric neurons and cells derived from an astrocytoma is reversible, as the protein's distribution and stability revert to the previous states when the proteasomal activity is restored. Thus, stabilization of ORF29p leads to its nuclear accumulation. Although proteasome inhibition induces ORF29p nuclear accumulation, this is not sufficient to reactivate latent VZV or target the immediate-early protein ORF62p to the nucleus in cultured guinea pig enteric neurons.

* Corresponding author. Mailing address: Department of Microbiology, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8149. Fax: (212) 305-5106. E-mail: sjs6{at}columbia.edu.

Journal of Virology, February 2006, p. 1497-1512, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1497-1512.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Walters, M. S., Kyratsous, C. A., Wan, S., Silverstein, S. (2008). Nuclear Import of the Varicella-Zoster Virus Latency-Associated Protein ORF63 in Primary Neurons Requires Expression of the Lytic Protein ORF61 and Occurs in a Proteasome-Dependent Manner. J. Virol. 82: 8673-8686 [Abstract] [Full Text]  
  • Kyratsous, C. A., Silverstein, S. J. (2007). BAG3, a Host Cochaperone, Facilitates Varicella-Zoster Virus Replication. J. Virol. 81: 7491-7503 [Abstract] [Full Text]  
  • Cohen, J. I., Krogmann, T., Pesnicak, L., Ali, M. A. (2007). Absence or Overexpression of the Varicella-Zoster Virus (VZV) ORF29 Latency-Associated Protein Impairs Late Gene Expression and Reduces VZV Latency in a Rodent Model. J. Virol. 81: 1586-1591 [Abstract] [Full Text]  
  • Stallings, C. L., Silverstein, S. J. (2006). Posttranslational Modification and Cell Type-Specific Degradation of Varicella-Zoster Virus ORF29p. J. Virol. 80: 10836-10846 [Abstract] [Full Text]  


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