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 Xiang, Y.
Right arrow Articles by Condit, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiang, Y.
Right arrow Articles by Condit, R. C.

 Previous Article  |  Next Article 

Journal of Virology, September 1998, p. 7012-7023, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Vaccinia Virus A18R DNA Helicase Is a Postreplicative Negative Transcription Elongation Factor

Ying Xiang,1 David A. Simpson,1,dagger Jason Spiegel,1,Dagger Aimin Zhou,2 Robert H. Silverman,2 and Richard C. Condit1,*

Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 32610-0266,1 and Department of Cancer Biology, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 441952

Received 16 April 1998/Accepted 21 May 1998

Loss of vaccinia virus A18R gene function results in an aberrant transcription profile termed promiscuous transcription, defined as transcription within regions of the genome which are normally transcriptionally silent late during infection. Promiscuous transcription results in an increase in the intracellular concentration of double-stranded RNA, which in turn results in activation of the cellular 2-5A pathway and subsequent RNase L-catalyzed degradation of viral and cellular RNAs. One of three hypotheses could account for promiscuous transcription: (i) reactivation of early promoters late during infection, (ii) random transcription initiation, (iii) readthrough transcription from upstream promoters. Transcriptional analysis of several viral genes, presented here, argues strongly against the first two hypotheses. We have tested the readthrough hypothesis by conducting a detailed transcriptional analysis of a region of the vaccinia virus genome which contains three early genes (M1L, M2L, and K1L) positioned directly downstream of the intermediate gene, K2L. The results show that mutation of the A18R gene results in increased readthrough transcription of the M1L gene originating from the K2L intermediate promoter. A18R mutant infection of RNase L knockout mouse fibroblast (KO3) cells does not result in 2-5A pathway activation, yet the virus mutant is defective in late viral gene expression and remains temperature sensitive. These results demonstrate that the A18R gene product is a negative transcription elongation factor for postreplicative viral genes.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610-0266. Phone: (352) 392-3128. Fax: (352) 392-3133. E-mail: condit{at}college.med.ufl.edu.

dagger Present address: Molecular Biology, Quidel Corporation, San Diego, CA 92121.

Dagger Present address: Department of Molecular Pharmacology, Memphis, TN 38105-2794.

Journal of Virology, September 1998, p. 7012-7023, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • D'Costa, S. M., Bainbridge, T. W., Condit, R. C. (2008). Purification and Properties of the Vaccinia Virus mRNA Processing Factor. J. Biol. Chem. 283: 5267-5275 [Abstract] [Full Text]  
  • Langland, J. O., Kash, J. C., Carter, V., Thomas, M. J., Katze, M. G., Jacobs, B. L. (2006). Suppression of Proinflammatory Signal Transduction and Gene Expression by the Dual Nucleic Acid Binding Domains of the Vaccinia Virus E3L Proteins.. J. Virol. 80: 10083-10095 [Abstract] [Full Text]  
  • Gedey, R., Jin, X.-L., Hinthong, O., Shisler, J. L. (2006). Poxviral Regulation of the Host NF-{kappa}B Response: the Vaccinia Virus M2L Protein Inhibits Induction of NF-{kappa}B Activation via an ERK2 Pathway in Virus-Infected Human Embryonic Kidney Cells.. J. Virol. 80: 8676-8685 [Abstract] [Full Text]  
  • Renn, C. N., Sanchez, D. J., Ochoa, M. T., Legaspi, A. J., Oh, C.-K., Liu, P. T., Krutzik, S. R., Sieling, P. A., Cheng, G., Modlin, R. L. (2006). TLR Activation of Langerhans Cell-Like Dendritic Cells Triggers an Antiviral Immune Response. J. Immunol. 177: 298-305 [Abstract] [Full Text]  
  • Jing, L., Chong, T. M., McClurkan, C. L., Huang, J., Story, B. T., Koelle, D. M. (2005). Diversity in the Acute CD8 T Cell Response to Vaccinia Virus in Humans. J. Immunol. 175: 7550-7559 [Abstract] [Full Text]  
  • Prins, C., Cresawn, S. G., Condit, R. C. (2004). An Isatin-{beta}-thiosemicarbazone-resistant Vaccinia Virus Containing a Mutation in the Second Largest Subunit of the Viral RNA Polymerase Is Defective in Transcription Elongation. J. Biol. Chem. 279: 44858-44871 [Abstract] [Full Text]  
  • Broyles, S. S., Kremer, M., Knutson, B. A. (2004). Antiviral Activity of Distamycin A against Vaccinia Virus Is the Result of Inhibition of Postreplicative mRNA Synthesis. J. Virol. 78: 2137-2141 [Abstract] [Full Text]  
  • Broyles, S. S. (2003). Vaccinia virus transcription. J. Gen. Virol. 84: 2293-2303 [Abstract] [Full Text]  
  • Xiang, Y., Condit, R. C., Vijaysri, S., Jacobs, B., Williams, B. R. G., Silverman, R. H. (2002). Blockade of Interferon Induction and Action by the E3L Double-Stranded RNA Binding Proteins of Vaccinia Virus. J. Virol. 76: 5251-5259 [Abstract] [Full Text]  
  • Afonso, C. L., Tulman, E. R., Lu, Z., Zsak, L., Kutish, G. F., Rock, D. L. (2000). The Genome of Fowlpox Virus. J. Virol. 74: 3815-3831 [Abstract] [Full Text]  
  • Lackner, C. A., Condit, R. C. (2000). Vaccinia Virus Gene A18R DNA Helicase Is a Transcript Release Factor. J. Biol. Chem. 275: 1485-1494 [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»