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 Zamora, M.
Right arrow Articles by Lloyd, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zamora, M.
Right arrow Articles by Lloyd, R. E.

 Previous Article  |  Next Article 

Journal of Virology, January 2002, p. 165-177, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.165-177.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Multiple eIF4GI-Specific Protease Activities Present in Uninfected and Poliovirus-Infected Cells

Miguel Zamora,1 Wilfred E. Marissen,1,2 and Richard E. Lloyd1*

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030,1 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731902

Received 2 February 2001/ Accepted 25 September 2001

Cleavage of eukaryotic translation initiation factor 4GI (eIF4GI) is required for shutoff of host cell translation during poliovirus (PV) infection of HeLa cells. Reports published by several groups have led to confusion whether this cleavage is mediated by viral 2A protease (2Apro) or a putative cellular enzyme (termed eIF4Gase) which is activated by 2Apro or other aspects of viral infection. Here we have further investigated eIF4Gase activities in PV-infected cells. Column purification of eIF4GI cleavage activity separated two activities which generated N-terminal cleavage products of different lengths. Both activities were detected using either native eIF4G or radiolabeled recombinant eIF4G as the substrate. Analysis of cleavage products formed by each activity on native and mutant substrates suggests that one activity cleaves eIF4G1 at or very near the 2Apro cleavage site and the other activity cleaves approximately 40 residues upstream of the 2Apro cleavage site. When PV infections in HeLa cells were supplemented with 2 mM guanidine, which indirectly limits expression of 2Apro, two distinct C-terminal cleavage fragments of eIF4GI were detected. These C-terminal cleavage fragments of eIF4GI were purified from infected cells, and a new eIF4GI cleavage site was mapped to a unique site 43 amino acids upstream of the known 2Apro cleavage site. Further, eIF4GI cleavage in vivo could be blocked by addition of zVAD to PV-guanidine infections. zVAD is a broad-spectrum caspase inhibitor which had no effect on 2Apro cleavage activity or PV polyprotein processing. Lastly, similar types of eIF4Gase cleavage activities were also detected in uninfected cells under various conditions, including early apoptosis or during cell cycle transit. The data suggest that the same types of eIF4GI cleavage activities which are generated in PV-infected cells can also be generated in the absence of virus. Taken together, the data support a model in which multiple cellular activities process eIF4GI in PV-infected cells, in addition to 2Apro.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-8993. Fax: (713) 798-5075. E-mail: rlloyd{at}bcm.tmc.edu.

Journal of Virology, January 2002, p. 165-177, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.165-177.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Burgon, T. B., Jenkins, J. A., Deitz, S. B., Spagnolo, J. F., Kirkegaard, K. (2009). Bypass Suppression of Small-Plaque Phenotypes by a Mutation in Poliovirus 2A That Enhances Apoptosis. J. Virol. 83: 10129-10139 [Abstract] [Full Text]  
  • Kaiser, C., Dobrikova, E. Y., Bradrick, S. S., Shveygert, M., Herbert, J. T., Gromeier, M. (2008). Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo. RNA 14: 2170-2182 [Abstract] [Full Text]  
  • Deszcz, L., Cencic, R., Sousa, C., Kuechler, E., Skern, T. (2006). An Antiviral Peptide Inhibitor That Is Active against Picornavirus 2A Proteinases but Not Cellular Caspases. J. Virol. 80: 9619-9627 [Abstract] [Full Text]  
  • Walsh, D., Perez, C., Notary, J., Mohr, I. (2005). Regulation of the Translation Initiation Factor eIF4F by Multiple Mechanisms in Human Cytomegalovirus-Infected Cells. J. Virol. 79: 8057-8064 [Abstract] [Full Text]  
  • Byrd, M. P., Zamora, M., Lloyd, R. E. (2005). Translation of Eukaryotic Translation Initiation Factor 4GI (eIF4GI) Proceeds from Multiple mRNAs Containing a Novel Cap-dependent Internal Ribosome Entry Site (IRES) That Is Active during Poliovirus Infection. J. Biol. Chem. 280: 18610-18622 [Abstract] [Full Text]  
  • Strong, R., Belsham, G. J. (2004). Sequential modification of translation initiation factor eIF4GI by two different foot-and-mouth disease virus proteases within infected baby hamster kidney cells: identification of the 3Cpro cleavage site. J. Gen. Virol. 85: 2953-2962 [Abstract] [Full Text]  
  • Belov, G. A., Lidsky, P. V., Mikitas, O. V., Egger, D., Lukyanov, K. A., Bienz, K., Agol, V. I. (2004). Bidirectional Increase in Permeability of Nuclear Envelope upon Poliovirus Infection and Accompanying Alterations of Nuclear Pores. J. Virol. 78: 10166-10177 [Abstract] [Full Text]  
  • Kuyumcu-Martinez, M., Belliot, G., Sosnovtsev, S. V., Chang, K.-O., Green, K. Y., Lloyd, R. E. (2004). Calicivirus 3C-Like Proteinase Inhibits Cellular Translation by Cleavage of Poly(A)-Binding Protein. J. Virol. 78: 8172-8182 [Abstract] [Full Text]  
  • Graham, K. L., Gustin, K. E., Rivera, C., Kuyumcu-Martinez, N. M., Choe, S. S., Lloyd, R. E., Sarnow, P., Utz, P. J. (2004). Proteolytic Cleavage of the Catalytic Subunit of DNA-Dependent Protein Kinase during Poliovirus Infection. J. Virol. 78: 6313-6321 [Abstract] [Full Text]  
  • Gradi, A., Foeger, N., Strong, R., Svitkin, Y. V., Sonenberg, N., Skern, T., Belsham, G. J. (2004). Cleavage of Eukaryotic Translation Initiation Factor 4GII within Foot-and-Mouth Disease Virus-Infected Cells: Identification of the L-Protease Cleavage Site In Vitro. J. Virol. 78: 3271-3278 [Abstract] [Full Text]  
  • VAN EDEN, M. E., BYRD, M. P., SHERRILL, K. W., LLOYD, R. E. (2004). Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress. RNA 10: 469-481 [Abstract] [Full Text]  
  • Kuyumcu-Martinez, N. M., Van Eden, M. E., Younan, P., Lloyd, R. E. (2004). Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Protease Inhibits Host Cell Translation: a Novel Mechanism for Host Translation Shutoff. Mol. Cell. Biol. 24: 1779-1790 [Abstract] [Full Text]  
  • Alvarez, E., Menendez-Arias, L., Carrasco, L. (2003). The Eukaryotic Translation Initiation Factor 4GI Is Cleaved by Different Retroviral Proteases. J. Virol. 77: 12392-12400 [Abstract] [Full Text]  
  • Sans, M. D., DiMagno, M. J., D'Alecy, L. G., Williams, J. A. (2003). Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G517-G528 [Abstract] [Full Text]  
  • Glaser, W., Triendl, A., Skern, T. (2003). The Processing of eIF4GI by Human Rhinovirus Type 2 2Apro: Relationship to Self-Cleavage and Role of Zinc. J. Virol. 77: 5021-5025 [Abstract] [Full Text]  
  • Foeger, N., Glaser, W., Skern, T. (2002). Recognition of Eukaryotic Initiation Factor 4G Isoforms by Picornaviral Proteinases. J. Biol. Chem. 277: 44300-44309 [Abstract] [Full Text]  
  • Byrd, M. P., Zamora, M., Lloyd, R. E. (2002). Generation of Multiple Isoforms of Eukaryotic Translation Initiation Factor 4GI by Use of Alternate Translation Initiation Codons. Mol. Cell. Biol. 22: 4499-4511 [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»