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 Lidsky, P. V.
Right arrow Articles by Agol, V. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lidsky, P. V.
Right arrow Articles by Agol, V. I.

 Previous Article  |  Next Article 

Journal of Virology, March 2006, p. 2705-2717, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2705-2717.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses

Peter V. Lidsky,1,{dagger} Stanleyson Hato,3,{dagger} Maryana V. Bardina,1,2,{dagger} Alexei G. Aminev,4 Ann C. Palmenberg,4 Eugene V. Sheval,2 Vladimir Y. Polyakov,2 Frank J. M. van Kuppeveld,3 and Vadim I. Agol1,2*

M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia,1 M. V. Lomonosov Moscow State University, Moscow 119899, Russia,2 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen 6500 HB, The Netherlands,3 Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin 537064

Received 13 August 2005/ Accepted 21 December 2005

Some picornaviruses, for example, poliovirus, increase bidirectional permeability of the nuclear envelope and suppress active nucleocytoplasmic transport. These activities require the viral protease 2Apro. Here, we studied nucleocytoplasmic traffic in cells infected with encephalomyocarditis virus (EMCV; a cardiovirus), which lacks the poliovirus 2Apro-related protein. EMCV similarly enhanced bidirectional nucleocytoplasmic traffic. By using the fluorescent "Timer" protein, which contains a nuclear localization signal, we showed that the cytoplasmic accumulation of nuclear proteins in infected cells was largely due to the nuclear efflux of "old" proteins rather than impaired active nuclear import of newly synthesized molecules. The nuclear envelope of digitonin-treated EMCV-infected cells permitted rapid efflux of a nuclear marker protein. Inhibitors of poliovirus 2Apro did not prevent the EMCV-induced efflux. Extracts from EMCV-infected cells and products of in vitro translation of viral RNAs contained an activity increasing permeability of the nuclear envelope of uninfected cells. This activity depended on the expression of the viral leader protein. Mutations disrupting the zinc finger motif of this protein abolished its efflux-inducing ability. Inactivation of the L protein phosphorylation site (Thr47->Ala) resulted in a delayed efflux, while a phosphorylation-mimicking (Thr47->Asp) replacement did not significantly impair the efflux-inducing ability. Such activity of extracts from EMCV-infected cells was suppressed by the protein kinase inhibitor staurosporine. As evidenced by electron microscopy, cardiovirus infection resulted in alteration of the nuclear pores, but it did not trigger degradation of the nucleoporins known to be degraded in the poliovirus-infected cells. Thus, two groups of picornaviruses, enteroviruses and cardioviruses, similarly alter the nucleocytoplasmic traffic but achieve this by strikingly different mechanisms.

* Corresponding author. Mailing address: Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia. Phone: 7 495 439 9026. Fax: 7 495 439 9321. E-mail: agol{at}belozersky.msu.ru.

{dagger} P.V.L., S.H., and M.V.B. contributed equally to this study.

Journal of Virology, March 2006, p. 2705-2717, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2705-2717.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cortes, R., Rosello-Lleti, E., Rivera, M., Martinez-Dolz, L., Salvador, A., Azorin, I., Portoles, M. (2009). Influence of heart failure on nucleocytoplasmic transport in human cardiomyocytes. Cardiovasc Res 0: cvp336v2-cvp336 [Abstract] [Full Text]  
  • Lawrence, P., Rieder, E. (2009). Identification of RNA Helicase A as a New Host Factor in the Replication Cycle of Foot-and-Mouth Disease Virus. J. Virol. 83: 11356-11366 [Abstract] [Full Text]  
  • Ricour, C., Borghese, F., Sorgeloos, F., Hato, S. V., van Kuppeveld, F. J. M., Michiels, T. (2009). Random Mutagenesis Defines a Domain of Theiler's Virus Leader Protein That Is Essential for Antagonism of Nucleocytoplasmic Trafficking and Cytokine Gene Expression. J. Virol. 83: 11223-11232 [Abstract] [Full Text]  
  • Castello, A., Izquierdo, J. M., Welnowska, E., Carrasco, L. (2009). RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage. J. Cell Sci. 122: 3799-3809 [Abstract] [Full Text]  
  • Lidsky, P. V., Romanova, L. I., Kolesnikova, M. S., Bardina, M. V., Khitrina, E. V., Hato, S. V., van Kuppeveld, F. J. M., Agol, V. I. (2009). Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma. J. Virol. 83: 9940-9951 [Abstract] [Full Text]  
  • Romanova, L. I., Lidsky, P. V., Kolesnikova, M. S., Fominykh, K. V., Gmyl, A. P., Sheval, E. V., Hato, S. V., van Kuppeveld, F. J. M., Agol, V. I. (2009). Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral "Security" Protein. J. Virol. 83: 7273-7284 [Abstract] [Full Text]  
  • Fan, J., Son, K.-N., Arslan, S. Y., Liang, Z., Lipton, H. L. (2009). Theiler's Murine Encephalomyelitis Virus Leader Protein Is the Only Nonstructural Protein Tested That Induces Apoptosis When Transfected into Mammalian Cells. J. Virol. 83: 6546-6553 [Abstract] [Full Text]  
  • Bardina, M. V., Lidsky, P. V., Sheval, E. V., Fominykh, K. V., van Kuppeveld, F. J. M., Polyakov, V. Y., Agol, V. I. (2009). Mengovirus-Induced Rearrangement of the Nuclear Pore Complex: Hijacking Cellular Phosphorylation Machinery. J. Virol. 83: 3150-3161 [Abstract] [Full Text]  
  • de los Santos, T., Diaz-San Segundo, F., Zhu, J., Koster, M., Dias, C. C. A., Grubman, M. J. (2009). A Conserved Domain in the Leader Proteinase of Foot-and-Mouth Disease Virus Is Required for Proper Subcellular Localization and Function. J. Virol. 83: 1800-1810 [Abstract] [Full Text]  
  • Porter, F. W., Palmenberg, A. C. (2009). Leader-Induced Phosphorylation of Nucleoporins Correlates with Nuclear Trafficking Inhibition by Cardioviruses. J. Virol. 83: 1941-1951 [Abstract] [Full Text]  
  • Pettit Kneller, E. L., Connor, J. H., Lyles, D. S. (2009). hnRNPs Relocalize to the Cytoplasm following Infection with Vesicular Stomatitis Virus. J. Virol. 83: 770-780 [Abstract] [Full Text]  
  • Ricour, C., Delhaye, S., Hato, S. V., Olenyik, T. D., Michel, B., van Kuppeveld, F. J. M., Gustin, K. E., Michiels, T. (2009). Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J. Gen. Virol. 90: 177-186 [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]  
  • Park, N., Katikaneni, P., Skern, T., Gustin, K. E. (2008). Differential Targeting of Nuclear Pore Complex Proteins in Poliovirus-Infected Cells. J. Virol. 82: 1647-1655 [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]  
  • de los Santos, T., Diaz-San Segundo, F., Grubman, M. J. (2007). Degradation of Nuclear Factor Kappa B during Foot-and-Mouth Disease Virus Infection. J. Virol. 81: 12803-12815 [Abstract] [Full Text]  
  • Perera, R., Daijogo, S., Walter, B. L., Nguyen, J. H. C., Semler, B. L. (2007). Cellular Protein Modification by Poliovirus: the Two Faces of Poly(rC)-Binding Protein. J. Virol. 81: 8919-8932 [Abstract] [Full Text]  
  • Wessels, E., Duijsings, D., Lanke, K. H. W., van Dooren, S. H. J., Jackson, C. L., Melchers, W. J. G., van Kuppeveld, F. J. M. (2006). Effects of Picornavirus 3A Proteins on Protein Transport and GBF1-Dependent COP-I Recruitment. J. Virol. 80: 11852-11860 [Abstract] [Full Text]  
  • Porter, F. W., Bochkov, Y. A., Albee, A. J., Wiese, C., Palmenberg, A. C. (2006). A picornavirus protein interacts with Ran-GTPase and disrupts nucleocytoplasmic transport. Proc. Natl. Acad. Sci. USA 103: 12417-12422 [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»