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 Hardy, R. W.
Right arrow Articles by Wertz, G. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hardy, R. W.
Right arrow Articles by Wertz, G. W.

 Previous Article  |  Next Article 

Journal of Virology, January 1999, p. 170-176, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Diverse Gene Junctions of Respiratory Syncytial Virus Modulate the Efficiency of Transcription Termination and Respond Differently to M2-Mediated Antitermination

Richard W. Hardy, Shawn B. Harmon, and Gail W. Wertz*

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294

Received 7 August 1998/Accepted 23 September 1998

The ability of the diverse gene junctions of respiratory syncytial (RS) virus to signal the termination of transcription was analyzed. Nine dicistronic subgenomic replicons of RS virus were constructed; each contained one of the RS virus gene junctions in its natural upstream and downstream sequence context. The RNA synthesis activities of these subgenomic replicons were analyzed in the absence and presence of the M2 protein, which we showed previously to function as a transcription antiterminator. Our data showed that the efficiency with which the polymerase terminated transcription was affected by the gene junction that it encountered. The M2 protein significantly decreased the efficiency of the termination of transcription, resulting in increased levels of readthrough transcription at all the gene junctions. The diverse gene junctions fell into three broad groups with respect to their ability to signal transcription termination. One group of gene junctions (NS1/NS2, NS2/N, M2/L, and L/trailer) showed inefficient termination in the absence or the presence of the M2 protein. A second group of gene junctions (N/P, P/M, M/SH, SH/G, and G/F) terminated transcription efficiently. The SH/G gene junction terminated transcription with the greatest efficiency and produced low levels of readthrough transcripts in the absence or the presence of the M2 protein, correlating with the absence of SH/G polycistronic transcripts in RS virus-infected cells. The F/M2 gene junction was particularly sensitive to the M2 protein: it efficiently signaled termination in the absence of the M2 protein but produced high levels of readthrough transcripts in the presence of the M2 protein. This result suggests that the M2 protein may regulate its own production by negative feedback. The data presented here show that the different gene junctions of RS virus do modulate RS virus transcription termination. The M2 protein reduced termination at all gene junctions. The magnitude of antitermination due to the M2 protein, however, varied at the different gene junctions. The data presented here indicate that the mechanism for the regulation of RS virus gene expression is more complex than was previously appreciated.

* Corresponding author. Mailing address: Department of Microbiology, University of Alabama at Birmingham, BBRB, Box 17, Room 366, 845 19th St. South, Birmingham, AL 35294. Phone: (205) 934-0877. Fax: (205) 934-1636. E-mail: gail_wertz{at}microbio.uab.edu.

Journal of Virology, January 1999, p. 170-176, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tran, T.-L., Castagne, N., Dubosclard, V., Noinville, S., Koch, E., Moudjou, M., Henry, C., Bernard, J., Yeo, R. P., Eleouet, J.-F. (2009). The Respiratory Syncytial Virus M2-1 Protein Forms Tetramers and Interacts with RNA and P in a Competitive Manner. J. Virol. 83: 6363-6374 [Abstract] [Full Text]  
  • Song, W., Liu, G., Bosworth, C. A., Walker, J. R., Megaw, G. A., Lazrak, A., Abraham, E., Sullender, W. M., Matalon, S. (2009). Respiratory Syncytial Virus Inhibits Lung Epithelial Na+ Channels by Up-regulating Inducible Nitric-oxide Synthase. J. Biol. Chem. 284: 7294-7306 [Abstract] [Full Text]  
  • Poenisch, M., Wille, S., Staeheli, P., Schneider, U. (2008). Polymerase Read-Through at the First Transcription Termination Site Contributes to Regulation of Borna Disease Virus Gene Expression. J. Virol. 82: 9537-9545 [Abstract] [Full Text]  
  • Li, D., Jans, D. A., Bardin, P. G., Meanger, J., Mills, J., Ghildyal, R. (2008). Association of Respiratory Syncytial Virus M Protein with Viral Nucleocapsids Is Mediated by the M2-1 Protein. J. Virol. 82: 8863-8870 [Abstract] [Full Text]  
  • Yan, Y., Samal, S. K. (2008). Role of Intergenic Sequences in Newcastle Disease Virus RNA Transcription and Pathogenesis. J. Virol. 82: 1323-1331 [Abstract] [Full Text]  
  • Boukhvalova, M. S., Prince, G. A., Blanco, J. C. G. (2007). Respiratory Syncytial Virus Infects and Abortively Replicates in the Lungs in Spite of Preexisting Immunity. J. Virol. 81: 9443-9450 [Abstract] [Full Text]  
  • Cowton, V. M., McGivern, D. R., Fearns, R. (2006). Unravelling the complexities of respiratory syncytial virus RNA synthesis. J. Gen. Virol. 87: 1805-1821 [Abstract] [Full Text]  
  • Cheng, X., Park, H., Zhou, H., Jin, H. (2005). Overexpression of the M2-2 Protein of Respiratory Syncytial Virus Inhibits Viral Replication. J. Virol. 79: 13943-13952 [Abstract] [Full Text]  
  • Liuzzi, M., Mason, S. W., Cartier, M., Lawetz, C., McCollum, R. S., Dansereau, N., Bolger, G., Lapeyre, N., Gaudette, Y., Lagace, L., Massariol, M.-J., Do, F., Whitehead, P., Lamarre, L., Scouten, E., Bordeleau, J., Landry, S., Rancourt, J., Fazal, G., Simoneau, B. (2005). Inhibitors of Respiratory Syncytial Virus Replication Target Cotranscriptional mRNA Guanylylation by Viral RNA-Dependent RNA Polymerase. J. Virol. 79: 13105-13115 [Abstract] [Full Text]  
  • Alvarez, R., Harrod, K. S., Shieh, W.-J., Zaki, S., Tripp, R. A. (2004). Human Metapneumovirus Persists in BALB/c Mice despite the Presence of Neutralizing Antibodies. J. Virol. 78: 14003-14011 [Abstract] [Full Text]  
  • Oomens, A. G. P., Wertz, G. W. (2004). trans-Complementation Allows Recovery of Human Respiratory Syncytial Viruses That Are Infectious but Deficient in Cell-to-Cell Transmission. J. Virol. 78: 9064-9072 [Abstract] [Full Text]  
  • Easton, A. J., Domachowske, J. B., Rosenberg, H. F. (2004). Animal Pneumoviruses: Molecular Genetics and Pathogenesis. Clin. Microbiol. Rev. 17: 390-412 [Abstract] [Full Text]  
  • Tran, K. C., Collins, P. L., Teng, M. N. (2004). Effects of Altering the Transcription Termination Signals of Respiratory Syncytial Virus on Viral Gene Expression and Growth In Vitro and In Vivo. J. Virol. 78: 692-699 [Abstract] [Full Text]  
  • Mason, S. W., Aberg, E., Lawetz, C., DeLong, R., Whitehead, P., Liuzzi, M. (2003). Interaction between Human Respiratory Syncytial Virus (RSV) M2-1 and P Proteins Is Required for Reconstitution of M2-1-Dependent RSV Minigenome Activity. J. Virol. 77: 10670-10676 [Abstract] [Full Text]  
  • Cartee, T. L., Megaw, A. G., Oomens, A. G. P., Wertz, G. W. (2003). Identification of a Single Amino Acid Change in the Human Respiratory Syncytial Virus L Protein That Affects Transcriptional Termination. J. Virol. 77: 7352-7360 [Abstract] [Full Text]  
  • Zhou, H., Cheng, X., Jin, H. (2003). Identification of Amino Acids That Are Critical to the Processivity Function of Respiratory Syncytial Virus M2-1 Protein. J. Virol. 77: 5046-5053 [Abstract] [Full Text]  
  • Oomens, A. G. P., Megaw, A. G., Wertz, G. W. (2003). Infectivity of a Human Respiratory Syncytial Virus Lacking the SH, G, and F Proteins Is Efficiently Mediated by the Vesicular Stomatitis Virus G Protein. J. Virol. 77: 3785-3798 [Abstract] [Full Text]  
  • Modrof, J., Becker, S., Muhlberger, E. (2003). Ebola Virus Transcription Activator VP30 Is a Zinc-Binding Protein. J. Virol. 77: 3334-3338 [Abstract] [Full Text]  
  • Neumann, G., Whitt, M. A., Kawaoka, Y. (2002). A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?. J. Gen. Virol. 83: 2635-2662 [Abstract] [Full Text]  
  • Weik, M., Modrof, J., Klenk, H.-D., Becker, S., Muhlberger, E. (2002). Ebola Virus VP30-Mediated Transcription Is Regulated by RNA Secondary Structure Formation. J. Virol. 76: 8532-8539 [Abstract] [Full Text]  
  • Lu, B., Brazas, R., Ma, C.-H., Kristoff, T., Cheng, X., Jin, H. (2002). Identification of Temperature-Sensitive Mutations in the Phosphoprotein of Respiratory Syncytial Virus That Are Likely Involved in Its Interaction with the Nucleoprotein. J. Virol. 76: 2871-2880 [Abstract] [Full Text]  
  • Cartee, T. L., Wertz, G. W. (2001). Respiratory Syncytial Virus M2-1 Protein Requires Phosphorylation for Efficient Function and Binds Viral RNA during Infection. J. Virol. 75: 12188-12197 [Abstract] [Full Text]  
  • Gubbay, O., Curran, J., Kolakofsky, D. (2001). Sendai virus genome synthesis and assembly are coupled: a possible mechanism to promote viral RNA polymerase processivity. J. Gen. Virol. 82: 2895-2903 [Abstract] [Full Text]  
  • Tang, R. S., Nguyen, N., Cheng, X., Jin, H. (2001). Requirement of Cysteines and Length of the Human Respiratory Syncytial Virus M2-1 Protein for Protein Function and Virus Viability. J. Virol. 75: 11328-11335 [Abstract] [Full Text]  
  • Parks, G. D., Ward, K. R., Rassa, J. C. (2001). Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis. J. Virol. 75: 2213-2223 [Abstract] [Full Text]  
  • Harmon, S. B., Megaw, A. G., Wertz, G. W. (2001). RNA Sequences Involved in Transcriptional Termination of Respiratory Syncytial Virus. J. Virol. 75: 36-44 [Abstract] [Full Text]  
  • Bukreyev, A., Murphy, B. R., Collins, P. L. (2000). Respiratory Syncytial Virus Can Tolerate an Intergenic Sequence of at Least 160 Nucleotides with Little Effect on Transcription or Replication In Vitro and In Vivo. J. Virol. 74: 11017-11026 [Abstract] [Full Text]  
  • Whelan, S. P. J., Barr, J. N., Wertz, G. W. (2000). Identification of a Minimal Size Requirement for Termination of Vesicular Stomatitis Virus mRNA: Implications for the Mechanism of Transcription. J. Virol. 74: 8268-8276 [Abstract] [Full Text]  
  • Finke, S., Cox, J. H., Conzelmann, K.-K. (2000). Differential Transcription Attenuation of Rabies Virus Genes by Intergenic Regions: Generation of Recombinant Viruses Overexpressing the Polymerase Gene. J. Virol. 74: 7261-7269 [Abstract] [Full Text]  
  • Hardy, R. W., Wertz, G. W. (2000). The Cys3-His1 Motif of the Respiratory Syncytial Virus M2-1 Protein Is Essential for Protein Function. J. Virol. 74: 5880-5885 [Abstract] [Full Text]  
  • Jin, H., Cheng, X., Zhou, H. Z. Y., Li, S., Seddiqui, A. (2000). Respiratory Syncytial Virus That Lacks Open Reading Frame 2 of the M2 Gene (M2-2) Has Altered Growth Characteristics and Is Attenuated in Rodents. J. Virol. 74: 74-82 [Abstract] [Full Text]  
  • Burke, E., Mahoney, N. M., Almo, S. C., Barik, S. (2000). Profilin Is Required for Optimal Actin-Dependent Transcription of Respiratory Syncytial Virus Genome RNA. J. Virol. 74: 669-675 [Abstract] [Full Text]  
  • He, B., Lamb, R. A. (1999). Effect of Inserting Paramyxovirus Simian Virus 5 Gene Junctions at the HN/L Gene Junction: Analysis of Accumulation of mRNAs Transcribed from Rescued Viable Viruses. J. Virol. 73: 6228-6234 [Abstract] [Full Text]  
  • Fearns, R., Collins, P. L. (1999). Role of the M2-1 Transcription Antitermination Protein of Respiratory Syncytial Virus in Sequential Transcription. J. Virol. 73: 5852-5864 [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»