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 Parks, G. D.
Right arrow Articles by Rassa, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Parks, G. D.
Right arrow Articles by Rassa, J. C.

 Previous Article  |  Next Article 

Journal of Virology, March 2001, p. 2213-2223, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2213-2223.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis

Griffith D. Parks,* Kimberly R. Ward, and John C. Rassadagger

Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1064

Received 19 September 2000/Accepted 17 November 2000

Recombinant simian virus 5 (rSV5) mutants containing substitutions in the M-F intergenic region were generated to determine the effect of increased readthrough transcription on the paramyxovirus growth cycle. We have previously shown, using an SV5 dicistronic minigenome, that replacement of the 22-base M-F intergenic region with a foreign sequence results in a template (Rep22) that directs very high levels of M-F readthrough transcription. An rSV5 containing the Rep22 substitution grew slower and to final titers that were 50- to 80-fold lower than those of wild-type (WT) rSV5. Cells infected with the Rep22 virus produced very low levels of monocistronic M and F mRNA, consistent with the M-F readthrough phenotype. Surprisingly, Rep22 virus-infected cells also displayed a global decrease in the accumulation of viral mRNA from genes located upstream and downstream of the M-F junction, and overall viral protein synthesis was reduced. Second-site revertants of the Rep22 virus that had regained WT transcription and growth properties contained a single base substitution that increased the M gene end U tract from four to eight residues, suggesting that the growth defects originated from higher-than-normal M-F readthrough transcription. Thus, the primary growth defect for the Rep22 virus appears to be in viral RNA synthesis and not in morphogenesis. A second rSV5 virus (G14), which contained a different foreign M-F intergenic sequence, grew to similar or slightly higher titers than WT rSV5 in some cell types and produced ~1.5- to 2-fold more mRNA and viral protein. The data support the hypothesis that inhibition of Rep22 virus growth is due to increased access by the polymerase to the 5' end of the genome and to the resulting overexpression of L protein. We propose that the elevated naturally occurring M-F readthrough which is characteristic of many paramyxoviruses serves as a mechanism to fine-tune the level of polymerase that is optimal for virus growth.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1064. Phone: (336) 716-9083. Fax: (336) 716-9928. E-mail: gparks{at}wfubmc.edu.

dagger Present address: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Journal of Virology, March 2001, p. 2213-2223, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2213-2223.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Anderson, D. E., von Messling, V. (2008). Region between the Canine Distemper Virus M and F Genes Modulates Virulence by Controlling Fusion Protein Expression. J. Virol. 82: 10510-10518 [Abstract] [Full Text]  
  • Pejawar-Gaddy, S., Alexander-Miller, M. A. (2006). Ligation of CD80 Is Critical for High-Level CD25 Expression on CD8+ T Lymphocytes. J. Immunol. 177: 4495-4502 [Abstract] [Full Text]  
  • Arimilli, S., Alexander-Miller, M. A., Parks, G. D. (2006). A Simian Virus 5 (SV5) P/V Mutant Is Less Cytopathic than Wild-Type SV5 in Human Dendritic Cells and Is a More Effective Activator of Dendritic Cell Maturation and Function.. J. Virol. 80: 3416-3427 [Abstract] [Full Text]  
  • Carlos, T. S., Fearns, R., Randall, R. E. (2005). Interferon-Induced Alterations in the Pattern of Parainfluenza Virus 5 Transcription and Protein Synthesis and the Induction of Virus Inclusion Bodies. J. Virol. 79: 14112-14121 [Abstract] [Full Text]  
  • Pejawar, S. S., Parks, G. D., Alexander-Miller, M. A. (2005). Abortive versus Productive Viral Infection of Dendritic Cells with a Paramyxovirus Results in Differential Upregulation of Select Costimulatory Molecules. J. Virol. 79: 7544-7557 [Abstract] [Full Text]  
  • Young, V. A., Parks, G. D. (2003). Simian Virus 5 Is a Poor Inducer of Chemokine Secretion from Human Lung Epithelial Cells: Identification of Viral Mutants That Activate Interleukin-8 Secretion by Distinct Mechanisms. J. Virol. 77: 7124-7130 [Abstract] [Full Text]  
  • Ayata, M., Komase, K., Shingai, M., Matsunaga, I., Katayama, Y., Ogura, H. (2002). Mutations Affecting Transcriptional Termination in the P Gene End of Subacute Sclerosing Panencephalitis Viruses. J. Virol. 76: 13062-13068 [Abstract] [Full Text]  
  • Wansley, E. K., Parks, G. D. (2002). Naturally Occurring Substitutions in the P/V Gene Convert the Noncytopathic Paramyxovirus Simian Virus 5 into a Virus That Induces Alpha/Beta Interferon Synthesis and Cell Death. J. Virol. 76: 10109-10121 [Abstract] [Full Text]  
  • Parks, G. D., Alexander-Miller, M. A. (2002). High avidity cytotoxic T lymphocytes to a foreign antigen are efficiently activated following immunization with a recombinant paramyxovirus, simian virus 5. J. Gen. Virol. 83: 1167-1172 [Abstract] [Full Text]  
  • Gray, P. M., Parks, G. D., Alexander-Miller, M. A. (2001). A Novel CD8-Independent High-Avidity Cytotoxic T-Lymphocyte Response Directed against an Epitope in the Phosphoprotein of the Paramyxovirus Simian Virus 5. J. Virol. 75: 10065-10072 [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»