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 Zoll, J. Articles by van Kuppeveld, F. J. M. Search for Related Content PubMed PubMed Citation Articles by Zoll, J. Articles by van Kuppeveld, F. J. M.

 Previous Article  |  Next Article 

Journal of Virology, October 2002, p. 9664-9672, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9664-9672.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Mengovirus Leader Protein Suppresses Alpha/Beta Interferon Production by Inhibition of the Iron/Ferritin-Mediated Activation of NF-B

Department of Medical Microbiology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands

Received 26 February 2002/ Accepted 25 June 2002

In our studies on the biological function of the mengovirus leader protein, we identified a casein kinase II (CK-2) phosphorylation site in the protein. Here we report that the mengovirus leader protein can be phosphorylated by CK-2 in vitro. Expression of a recombinant leader protein in which the consensus CK-2 sequence around threonine 47 was disturbed resulted in a mutant protein that could no longer be phosphorylated. The CK-2 consensus sequence was modified by site-directed mutagenesis and subsequently introduced into a mengovirus cDNA clone to investigate the effect of the phosphorylation of the leader protein on virus replication and on the host cell response. Modifications by which the CK-2 consensus sequence was disturbed resulted in mutant viruses with reduced growth kinetics. We demonstrated that the integrity of the CK-2 phosphorylation site of the mengovirus leader protein was specifically related to the suppression of NF-B activation and subsequent suppression of alpha/beta interferon production in infected cells. We also found that the integrity of the CK-2 phosphorylation site of the leader protein coincided with an increase of ferritin expression in the infected cell. These data indicate that the leader protein suppresses the iron-mediated activation of NF-B and thereby inhibits alpha/beta interferon expression in the infected cell.

This article has been cited by other articles:

• 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]  
• 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]  
• Versteeg, G. A., Slobodskaya, O., Spaan, W. J. M. (2006). Transcriptional profiling of acute cytopathic murine hepatitis virus infection in fibroblast-like cells. J. Gen. Virol. 87: 1961-1975 [Abstract] [Full Text]  
• Paul, S., Michiels, T. (2006). Cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness.. J. Gen. Virol. 87: 1237-1246 [Abstract] [Full Text]  
• Lidsky, P. V., Hato, S., Bardina, M. V., Aminev, A. G., Palmenberg, A. C., Sheval, E. V., Polyakov, V. Y., van Kuppeveld, F. J. M., Agol, V. I. (2006). Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses. J. Virol. 80: 2705-2717 [Abstract] [Full Text]  
• de los Santos, T., de Avila Botton, S., Weiblen, R., Grubman, M. J. (2006). The Leader Proteinase of Foot-and-Mouth Disease Virus Inhibits the Induction of Beta Interferon mRNA and Blocks the Host Innate Immune Response. J. Virol. 80: 1906-1914 [Abstract] [Full Text]  
• Gil, L. H. V. G., Ansari, I. H., Vassilev, V., Liang, D., Lai, V. C. H., Zhong, W., Hong, Z., Dubovi, E. J., Donis, R. O. (2006). The Amino-Terminal Domain of Bovine Viral Diarrhea Virus Npro Protein Is Necessary for Alpha/Beta Interferon Antagonism. J. Virol. 80: 900-911 [Abstract] [Full Text]  
• Spiegel, M., Pichlmair, A., Martinez-Sobrido, L., Cros, J., Garcia-Sastre, A., Haller, O., Weber, F. (2005). Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3. J. Virol. 79: 2079-2086 [Abstract] [Full Text]  
• Delhaye, S., van Pesch, V., Michiels, T. (2004). The Leader Protein of Theiler's Virus Interferes with Nucleocytoplasmic Trafficking of Cellular Proteins. J. Virol. 78: 4357-4362 [Abstract] [Full Text]  
• Sasaki, J., Nagashima, S., Taniguchi, K. (2003). Aichi Virus Leader Protein Is Involved in Viral RNA Replication and Encapsidation. J. Virol. 77: 10799-10807 [Abstract] [Full Text]  
• Arieh, S. V.-B., Laham, N., Schechter, C., Yewdell, J. W., Coligan, J. E., Ehrlich, R. (2003). A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules. Blood 101: 2858-2864 [Abstract] [Full Text]