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 Schwartz, J. A.
Right arrow Articles by Silverstein, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwartz, J. A.
Right arrow Articles by Silverstein, S. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2006, p. 769-784, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.769-784.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

UL54-Null Pseudorabies Virus Is Attenuated in Mice but Productively Infects Cells in Culture

Jennifer A. Schwartz,1 Elizabeth E. Brittle,2 Ashley E. Reynolds,2 Lynn W. Enquist,2 and Saul J. Silverstein1*

Department of Microbiology, Columbia University, New York, New York 10032,1 Department of Molecular Biology, Princeton University, Princeton, New Jersey 085442

Received 22 April 2005/ Accepted 19 October 2005

The pseudorabies virus (PRV) UL54 homologs are important multifunctional proteins with roles in shutoff of host protein synthesis, transactivation of virus and cellular genes, and regulation of splicing and translation. Here we describe the first genetic characterization of UL54. We constructed UL54 null mutations in a PRV bacterial artificial chromosome using sugar suicide and {lambda}Red allele exchange systems. Surprisingly, UL54 is dispensable for growth in tissue culture but exhibits a small-plaque phenotype that can be complemented in trans by both the herpes simplex virus type 1 ICP27 and varicella-zoster virus open reading frame 4 proteins. Deletion of UL54 in the virus vJS{Delta}54 had no effect on the ability of the virus to shut off host cell protein synthesis but did affect virus gene expression. The glycoprotein gC accumulated to lower levels in cells infected with vJS{Delta}54 compared to those infected with wild-type virus, while gK levels were undetectable. Other late gene products, gB, gE, and Us9, accumulated to higher levels than those seen in cells infected with wild-type virus in a multiplicity-dependent manner. DNA replication is also reduced in cells infected with vJS{Delta}54. UL54 appears to regulate UL53 and UL52 at the transcriptional level as their respective RNAs are decreased in cells infected with vJS{Delta}54. Interestingly, vJS{Delta}54 is highly attenuated in a mouse model of PRV infection. Animals infected with vJS{Delta}54 survive twice as long as animals infected with wild-type virus, and this results in delayed accumulation of virus-specific antigens in skin, dorsal root ganglia, and spinal cord tissues.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, 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, January 2006, p. 769-784, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.769-784.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Skiba, M., Mettenleiter, T. C., Karger, A. (2008). Quantitative Whole-Cell Proteome Analysis of Pseudorabies Virus-Infected Cells. J. Virol. 82: 9689-9699 [Abstract] [Full Text]  
  • Storlie, J., Jackson, W., Hutchinson, J., Grose, C. (2006). Delayed Biosynthesis of Varicella-Zoster Virus Glycoprotein C: Upregulation by Hexamethylene Bisacetamide and Retinoic Acid Treatment of Infected Cells. J. Virol. 80: 9544-9556 [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»