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 Campbell Dwyer, E. J.
Right arrow Articles by Borden, K. L. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Campbell Dwyer, E. J.
Right arrow Articles by Borden, K. L. B.

 Previous Article  |  Next Article 

Journal of Virology, April 2000, p. 3293-3300, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Lymphocytic Choriomeningitis Virus RING Protein Z Associates with Eukaryotic Initiation Factor 4E and Selectively Represses Translation in a RING-Dependent Manner

Elizabeth J. Campbell Dwyer,1 HuiKang Lai,2 Rhea C. MacDonald,1,2 Maria S. Salvato,3 and Katherine L. B. Borden1,2,*

Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H71; Department of Physiology and Biophysics, Mt. Sinai School of Medicine, New York, New York 100292; and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706-15323

Received 26 July 1999/Accepted 30 December 1999

Only a few host cell proteins that associate with arenaviruses have been identified. To date, the arenavirus Z protein associates with the promyelocytic leukemia protein PML and the ribosomal P proteins. The majority of PML is present in nuclear bodies which are translocated to the cytoplasm by infection with the arenavirus, lymphocytic choriomeningitis virus (LCMV). The Z protein is a small zinc-binding RING protein with an unknown function which is required for the viral life cycle. Here, we demonstrate an association between Z and the host cell translation factor, eukaryotic initiation factor 4E (eIF-4E) in infected and transfected cells. Z's association with both ribosomal proteins and this translation factor led us to investigate whether Z could modulate host cell translation. In cell culture, Z selectively represses protein production in an eIF-4E-dependent manner. Specifically, we see reduction in cyclin D1 protein production with no effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cells transfected with Z. Previous reports indicate that cyclin D1 is sensitive to eIF-4E levels, whereas GAPDH is not. Consistent with this, we observe preferential downregulation of cyclin D1 during infection and no effect on GAPDH. Further, no changes in RNA levels were observed for cyclin D1 or GAPDH transcripts. The interaction between eIF-4E and Z may provide a mechanism for slower growth observed in infected cells and a viral strategy for establishing chronic infection.


* Corresponding author. Mailing address: Department of Physiology and Biophysics, Mt. Sinai School of Medicine, One Gustave Levy Pl., New York, NY 10029-6574. Phone: (212) 659-8677. Fax: (212) 849-2456. E-mail: kathyb{at}inka.mssm.edu.


Journal of Virology, April 2000, p. 3293-3300, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Wilda, M., Lopez, N., Casabona, J. C., Franze-Fernandez, M. T. (2008). Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding. J. Virol. 82: 11454-11460 [Abstract] [Full Text]  
  • Gainey, M. D., Dillon, P. J., Clark, K. M., Manuse, M. J., Parks, G. D. (2008). Paramyxovirus-Induced Shutoff of Host and Viral Protein Synthesis: Role of the P and V Proteins in Limiting PKR Activation. J. Virol. 82: 828-839 [Abstract] [Full Text]  
  • Djavani, M. M., Crasta, O. R., Zapata, J. C., Fei, Z., Folkerts, O., Sobral, B., Swindells, M., Bryant, J., Davis, H., Pauza, C. D., Lukashevich, I. S., Hammamieh, R., Jett, M., Salvato, M. S. (2007). Early Blood Profiles of Virus Infection in a Monkey Model for Lassa Fever. J. Virol. 81: 7960-7973 [Abstract] [Full Text]  
  • Garcia, C. C., Djavani, M., Topisirovic, I., Borden, K. L. B., Salvato, M. S., Damonte, E. B. (2006). Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds.. J. Gen. Virol. 87: 1217-1228 [Abstract] [Full Text]  
  • Sanchez, A. B., de la Torre, J. C. (2005). Genetic and Biochemical Evidence for an Oligomeric Structure of the Functional L Polymerase of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus. J. Virol. 79: 7262-7268 [Abstract] [Full Text]  
  • Djavani, M., Topisirovic, I., Zapata, J. C., Sadowska, M., Yang, Y., Rodas, J., Lukashevich, I. S., Bogue, C. W., Pauza, C. D., Borden, K. L. B., Salvato, M. S. (2005). The Proline-Rich Homeodomain (PRH/HEX) Protein Is Down-Regulated in Liver during Infection with Lymphocytic Choriomeningitis Virus. J. Virol. 79: 2461-2473 [Abstract] [Full Text]  
  • Kentsis, A., Topisirovic, I., Culjkovic, B., Shao, L., Borden, K. L. B. (2004). Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc. Natl. Acad. Sci. USA 101: 18105-18110 [Abstract] [Full Text]  
  • Perez, M., Greenwald, D. L., de La Torre, J. C. (2004). Myristoylation of the RING Finger Z Protein Is Essential for Arenavirus Budding. J. Virol. 78: 11443-11448 [Abstract] [Full Text]  
  • Leonard, S., Viel, C., Beauchemin, C., Daigneault, N., Fortin, M. G., Laliberte, J.-F. (2004). Interaction of VPg-Pro of Turnip mosaic virus with the translation initiation factor 4E and the poly(A)-binding protein in planta. J. Gen. Virol. 85: 1055-1063 [Abstract] [Full Text]  
  • Cornu, T. I., Feldmann, H., de la Torre, J. C. (2004). Cells Expressing the RING Finger Z Protein Are Resistant to Arenavirus Infection. J. Virol. 78: 2979-2983 [Abstract] [Full Text]  
  • Baize, S., Kaplon, J., Faure, C., Pannetier, D., Georges-Courbot, M.-C., Deubel, V. (2004). Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells. J. Immunol. 172: 2861-2869 [Abstract] [Full Text]  
  • Perez, M., Craven, R. C., de la Torre, J. C. (2003). The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies. Proc. Natl. Acad. Sci. USA 100: 12978-12983 [Abstract] [Full Text]  
  • Strecker, T., Eichler, R., Meulen, J. t., Weissenhorn, W., Dieter Klenk, H., Garten, W., Lenz, O. (2003). Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles. J. Virol. 77: 10700-10705 [Abstract] [Full Text]  
  • Lukashevich, I. S., Tikhonov, I., Rodas, J. D., Zapata, J. C., Yang, Y., Djavani, M., Salvato, M. S. (2003). Arenavirus-Mediated Liver Pathology: Acute Lymphocytic Choriomeningitis Virus Infection of Rhesus Macaques Is Characterized by High-Level Interleukin-6 Expression and Hepatocyte Proliferation. J. Virol. 77: 1727-1737 [Abstract] [Full Text]  
  • Kentsis, A., Gordon, R. E., Borden, K. L. B. (2002). Control of biochemical reactions through supramolecular RING domain self-assembly. Proc. Natl. Acad. Sci. USA 99: 15404-15409 [Abstract] [Full Text]  
  • Topisirovic, I., Capili, A. D., Borden, K. L. B. (2002). Gamma Interferon and Cadmium Treatments Modulate Eukaryotic Initiation Factor 4E-Dependent mRNA Transport of Cyclin D1 in a PML-Dependent Manner. Mol. Cell. Biol. 22: 6183-6198 [Abstract] [Full Text]  
  • Borden, K. L. B. (2002). Pondering the Promyelocytic Leukemia Protein (PML) Puzzle: Possible Functions for PML Nuclear Bodies. Mol. Cell. Biol. 22: 5259-5269 [Full Text]  
  • Cornu, T. I., de la Torre, J. C. (2002). Characterization of the Arenavirus RING Finger Z Protein Regions Required for Z-Mediated Inhibition of Viral RNA Synthesis. J. Virol. 76: 6678-6688 [Abstract] [Full Text]  
  • Lee, K. J., Perez, M., Pinschewer, D. D., de la Torre, J. C. (2002). Identification of the Lymphocytic Choriomeningitis Virus (LCMV) Proteins Required To Rescue LCMV RNA Analogs into LCMV-Like Particles. J. Virol. 76: 6393-6397 [Abstract] [Full Text]  
  • Bonilla, W. V., Pinschewer, D. D., Klenerman, P., Rousson, V., Gaboli, M., Pandolfi, P. P., Zinkernagel, R. M., Salvato, M. S., Hengartner, H. (2002). Effects of Promyelocytic Leukemia Protein on Virus-Host Balance. J. Virol. 76: 3810-3818 [Abstract] [Full Text]  
  • Kentsis, A., Gordon, R. E., Borden, K. L. B. (2002). From the Cover: Self-assembly properties of a model RING domain. Proc. Natl. Acad. Sci. USA 99: 667-672 [Abstract] [Full Text]  
  • Lopez, N., Jacamo, R., Franze-Fernandez, M. T. (2001). Transcription and RNA Replication of Tacaribe Virus Genome and Antigenome Analogs Require N and L Proteins: Z Protein Is an Inhibitor of These Processes. J. Virol. 75: 12241-12251 [Abstract] [Full Text]  
  • Cornu, T. I., de la Torre, J. C. (2001). RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome. J. Virol. 75: 9415-9426 [Abstract] [Full Text]  
  • Djavani, M., Rodas, J., Lukashevich, I. S., Horejsh, D., Pandolfi, P. P., Borden, K. L. B., Salvato, M. S. (2001). Role of the Promyelocytic Leukemia Protein PML in the Interferon Sensitivity of Lymphocytic Choriomeningitis Virus. J. Virol. 75: 6204-6208 [Abstract] [Full Text]  
  • Kentsis, A., Gordon, R. E., Borden, K. L. B. (2002). From the Cover: Self-assembly properties of a model RING domain. Proc. Natl. Acad. Sci. USA 99: 667-672 [Abstract] [Full Text]