This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jácamo, R. Articles by Franze-Fernández, M. T. Search for Related Content PubMed PubMed Citation Articles by Jácamo, R. Articles by Franze-Fernández, M. T.

Tacaribe Virus Z Protein Interacts with the L Polymerase Protein To Inhibit Viral RNA Synthesis

Centro de Virología Animal (CONICET), C1414DEM Buenos Aires, Argentina

Received 16 April 2003/ Accepted 9 July 2003

Tacaribe virus (TV) is the prototype of the New World group of arenaviruses. The TV genome encodes four proteins, the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a small RING finger protein (Z). Using a reverse genetic system, we recently demonstrated that TV N and L are sufficient to drive transcription and full-cycle RNA replication mediated by TV-like RNAs and that Z is a powerful inhibitor of these processes (N. López, R. Jácamo, and M. T. Franze-Fernández, J. Virol. 65:12241-12251, 2001). In the present study we investigated whether Z might interact with either of the proteins, N and L, required for RNA synthesis. To that end, we used coimmunoprecipitation with monospecific antibodies against the viral proteins and coimmunoprecipitation with serum against glutathione S-transferase (GST) and binding to glutathione-Sepharose beads when Z was expressed as a fusion protein with GST. We demonstrated that Z interacted with L but not with N and that Z inhibitory activity was dependent on its ability to bind to L. We also evaluated the contribution of different Z regions to its binding ability and functional activity. We found that integrity of the RING structure is essential for Z binding to L and for Z inhibitory activity. Mutants with deletions at the N and C termini of Z showed that amino acids within the C-terminal region and immediately adjacent to the RING domain N terminus contribute to efficient Z-L interaction and are required for inhibitory activity. The data presented here provide the first evidence of an interaction between Z and L, suggesting that Z interferes with viral RNA synthesis by direct interaction with L. In addition, coimmunoprecipitation studies revealed a previously unreported interaction between N and L.

This article has been cited by other articles:

• Ellenberg, P., Linero, F. N., Scolaro, L. A. (2007). Superinfection exclusion in BHK-21 cells persistently infected with Junin virus. J. Gen. Virol. 88: 2730-2739 [Abstract] [Full Text]  
• Yi, G., Gopinath, K., Kao, C. C. (2007). Selective Repression of Translation by the Brome Mosaic Virus 1a RNA Replication Protein. J. Virol. 81: 1601-1609 [Abstract] [Full Text]  
• Martinez-Sobrido, L., Zuniga, E. I., Rosario, D., Garcia-Sastre, A., de la Torre, J. C. (2006). Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus.. J. Virol. 80: 9192-9199 [Abstract] [Full Text]  
• Rey, O., Papazyan, R., Waldron, R. T., Young, S. H., Lippincott-Schwartz, J., Jacamo, R., Rozengurt, E. (2006). The Nuclear Import of Protein Kinase D3 Requires Its Catalytic Activity. J. Biol. Chem. 281: 5149-5157 [Abstract] [Full Text]  
• Neuman, B. W., Adair, B. D., Burns, J. W., Milligan, R. A., Buchmeier, M. J., Yeager, M. (2005). Complementarity in the Supramolecular Design of Arenaviruses and Retroviruses Revealed by Electron Cryomicroscopy and Image Analysis. J. Virol. 79: 3822-3830 [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]  
• Hass, M., Golnitz, U., Muller, S., Becker-Ziaja, B., Gunther, S. (2004). Replicon System for Lassa Virus. J. Virol. 78: 13793-13803 [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]