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 Garmashova, N.
Right arrow Articles by Frolov, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garmashova, N.
Right arrow Articles by Frolov, I.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 5686-5696, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02739-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Sindbis Virus Nonstructural Protein nsP2 Is Cytotoxic and Inhibits Cellular Transcription

Natalia Garmashova,1 Rodion Gorchakov,1 Elena Frolova,1,2 and Ilya Frolov1*

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1019,1 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-10722

Received 30 December 2005/ Accepted 21 March 2006

Replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (CPE) and cell death. Sindbis virus (SIN) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mRNAs and rRNAs plays a critical role. SIN nonstructural protein nsP2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in the carboxy-terminal part of nsP2 could make SIN and other alphaviruses and replicons less cytopathic and capable of persisting in some vertebrate cell lines. These mutants were incapable of inhibiting transcription and downregulating a viral stress-induced cell response. In the present work, we demonstrate that (i) SIN nsP2 is critically involved in CPE development, not only during the replication of SIN-specific RNAs, but also when this protein is expressed alone from different expression cassettes; (ii) the cytotoxic effect of SIN nsP2 appears to be at least partially determined by its ability to cause transcriptional shutoff; (iii) these functions of SIN nsP2 are determined by the integrity of the carboxy-terminal peptide of this protein located outside its helicase and protease domains, rather than by its protease activity; and (iv) the cytotoxic activity of SIN nsP2 depends on the presence of this protein in a free form, and alterations in P123 processing abolish the ability of nsP2 to cause CPE.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019. Phone: (409) 772-2327. Fax: (409) 772-5065. E-mail: ivfrolov{at}utmb.edu.

Journal of Virology, June 2006, p. 5686-5696, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02739-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Simmons, J. D., White, L. J., Morrison, T. E., Montgomery, S. A., Whitmore, A. C., Johnston, R. E., Heise, M. T. (2009). Venezuelan Equine Encephalitis Virus Disrupts STAT1 Signaling by Distinct Mechanisms Independent of Host Shutoff. J. Virol. 83: 10571-10581 [Abstract] [Full Text]  
  • Yin, J., Gardner, C. L., Burke, C. W., Ryman, K. D., Klimstra, W. B. (2009). Similarities and Differences in Antagonism of Neuron Alpha/Beta Interferon Responses by Venezuelan Equine Encephalitis and Sindbis Alphaviruses. J. Virol. 83: 10036-10047 [Abstract] [Full Text]  
  • Frolov, I., Garmashova, N., Atasheva, S., Frolova, E. I. (2009). Random Insertion Mutagenesis of Sindbis Virus Nonstructural Protein 2 and Selection of Variants Incapable of Downregulating Cellular Transcription. J. Virol. 83: 9031-9044 [Abstract] [Full Text]  
  • Mai, J., Sawicki, S. G., Sawicki, D. L. (2009). Fate of Minus-Strand Templates and Replication Complexes Produced by a P23-Cleavage-Defective Mutant of Sindbis Virus. J. Virol. 83: 8553-8564 [Abstract] [Full Text]  
  • Gorchakov, R., Garmashova, N., Frolova, E., Frolov, I. (2008). Different Types of nsP3-Containing Protein Complexes in Sindbis Virus-Infected Cells. J. Virol. 82: 10088-10101 [Abstract] [Full Text]  
  • Mayuri, , Geders, T. W., Smith, J. L., Kuhn, R. J. (2008). Role for Conserved Residues of Sindbis Virus Nonstructural Protein 2 Methyltransferase-Like Domain in Regulation of Minus-Strand Synthesis and Development of Cytopathic Infection. J. Virol. 82: 7284-7297 [Abstract] [Full Text]  
  • Aguilar, P. V., Leung, L. W., Wang, E., Weaver, S. C., Basler, C. F. (2008). A Five-Amino-Acid Deletion of the Eastern Equine Encephalitis Virus Capsid Protein Attenuates Replication in Mammalian Systems but Not in Mosquito Cells. J. Virol. 82: 6972-6983 [Abstract] [Full Text]  
  • Gorchakov, R., Frolova, E., Sawicki, S., Atasheva, S., Sawicki, D., Frolov, I. (2008). A New Role for ns Polyprotein Cleavage in Sindbis Virus Replication. J. Virol. 82: 6218-6231 [Abstract] [Full Text]  
  • Kiiver, K., Tagen, I., Zusinaite, E., Tamberg, N., Fazakerley, J. K., Merits, A. (2008). Properties of non-structural protein 1 of Semliki Forest virus and its interference with virus replication. J. Gen. Virol. 89: 1457-1466 [Abstract] [Full Text]  
  • Atasheva, S., Garmashova, N., Frolov, I., Frolova, E. (2008). Venezuelan Equine Encephalitis Virus Capsid Protein Inhibits Nuclear Import in Mammalian but Not in Mosquito Cells. J. Virol. 82: 4028-4041 [Abstract] [Full Text]  
  • Tamm, K., Merits, A., Sarand, I. (2008). Mutations in the nuclear localization signal of nsP2 influencing RNA synthesis, protein expression and cytotoxicity of Semliki Forest virus. J. Gen. Virol. 89: 676-686 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
  • Slobodskaya, O., Laarman, A., Spaan, W. J. M. (2008). Intracellular Restriction of a Productive Noncytopathic Coronavirus Infection. J. Virol. 82: 451-460 [Abstract] [Full Text]  
  • Garmashova, N., Atasheva, S., Kang, W., Weaver, S. C., Frolova, E., Frolov, I. (2007). Analysis of Venezuelan Equine Encephalitis Virus Capsid Protein Function in the Inhibition of Cellular Transcription. J. Virol. 81: 13552-13565 [Abstract] [Full Text]  
  • Montgomery, S. A., Johnston, R. E. (2007). Nuclear Import and Export of Venezuelan Equine Encephalitis Virus Nonstructural Protein 2. J. Virol. 81: 10268-10279 [Abstract] [Full Text]  
  • Breakwell, L., Dosenovic, P., Karlsson Hedestam, G. B., D'Amato, M., Liljestrom, P., Fazakerley, J., McInerney, G. M. (2007). Semliki Forest Virus Nonstructural Protein 2 Is Involved in Suppression of the Type I Interferon Response. J. Virol. 81: 8677-8684 [Abstract] [Full Text]  
  • Atasheva, S., Gorchakov, R., English, R., Frolov, I., Frolova, E. (2007). Development of Sindbis Viruses Encoding nsP2/GFP Chimeric Proteins and Their Application for Studying nsP2 Functioning. J. Virol. 81: 5046-5057 [Abstract] [Full Text]  
  • Aguilar, P. V., Weaver, S. C., Basler, C. F. (2007). Capsid Protein of Eastern Equine Encephalitis Virus Inhibits Host Cell Gene Expression. J. Virol. 81: 3866-3876 [Abstract] [Full Text]  
  • Garmashova, N., Gorchakov, R., Volkova, E., Paessler, S., Frolova, E., Frolov, I. (2007). The Old World and New World Alphaviruses Use Different Virus-Specific Proteins for Induction of Transcriptional Shutoff. J. Virol. 81: 2472-2484 [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»