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 Martínez-Sobrido, L.
Right arrow Articles by de la Torre, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martínez-Sobrido, L.
Right arrow Articles by de la Torre, J. C.

 Previous Article  |  Next Article 

Journal of Virology, September 2006, p. 9192-9199, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00555-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of the Type I Interferon Response by the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus

Luis Martínez-Sobrido,1 Elina I. Zúñiga,2 Debralee Rosario,2 Adolfo García-Sastre,1 and Juan Carlos de la Torre2*

Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029,1 Molecular Integrative Neuroscience Department (MIND), The Scripps Research Institute, La Jolla, California 920372

Received 16 March 2006/ Accepted 29 June 2006

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a formidable battle horse for the study of viral immunology, as well as viral persistence and associated diseases. Investigations with LCMV have uncovered basic mechanisms by which viruses avoid elimination by the host adaptive immune response. In this study we show that LCMV also disables the host innate defense by interfering with beta interferon (IFN-ß) production in response to different stimuli, including infection with Sendai virus and liposome-mediated DNA transfection. Inhibition of IFN production in LCMV-infected cells was caused by an early block in the IFN regulatory factor 3 (IRF-3) activation pathway. This defect was restored in cells cured of LCMV, indicating that one or more LCMV products are responsible for the inhibition of IRF-3 activation. Using expression plasmids encoding individual LCMV proteins, we found that expression of the LCMV nucleoprotein (NP) was sufficient to inhibit both IFN production and nuclear translocation of IRF-3. To our knowledge, this is the first evidence of an IFN-counteracting viral protein in the Arenaviridae family. Inhibition of IFN production by the arenavirus NP is likely to be a determinant of virulence in vivo.

* Corresponding author. Mailing address: Molecular Integrative Neuroscience Department (MIND), The Scripps Research Institute, IMM-6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9462. Fax: (858) 784-9981. E-mail: juanct{at}scripps.edu.

Journal of Virology, September 2006, p. 9192-9199, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00555-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Martinez-Sobrido, L., Emonet, S., Giannakas, P., Cubitt, B., Garcia-Sastre, A., de la Torre, J. C. (2009). Identification of Amino Acid Residues Critical for the Anti-Interferon Activity of the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus. J. Virol. 83: 11330-11340 [Abstract] [Full Text]  
  • Lee, L. N., Burke, S., Montoya, M., Borrow, P. (2009). Multiple Mechanisms Contribute to Impairment of Type 1 Interferon Production during Chronic Lymphocytic Choriomeningitis Virus Infection of Mice. J. Immunol. 182: 7178-7189 [Abstract] [Full Text]  
  • Bowick, G. C., Spratt, H. M., Hogg, A. E., Endsley, J. J., Wiktorowicz, J. E., Kurosky, A., Luxon, B. A., Gorenstein, D. G., Herzog, N. K. (2009). Analysis of the Differential Host Cell Nuclear Proteome Induced by Attenuated and Virulent Hemorrhagic Arenavirus Infection. J. Virol. 83: 687-700 [Abstract] [Full Text]  
  • Strong, J. E., Wong, G., Jones, S. E., Grolla, A., Theriault, S., Kobinger, G. P., Feldmann, H. (2008). Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway. Proc. Natl. Acad. Sci. USA 105: 17982-17987 [Abstract] [Full Text]  
  • Hai, R., Martinez-Sobrido, L., Fraser, K. A., Ayllon, J., Garcia-Sastre, A., Palese, P. (2008). Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach. J. Virol. 82: 10580-10590 [Abstract] [Full Text]  
  • Scott, E. P., Aronson, J. F. (2008). Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs. J. Gen. Virol. 89: 2569-2579 [Abstract] [Full Text]  
  • Munoz-Fontela, C., Macip, S., Martinez-Sobrido, L., Brown, L., Ashour, J., Garcia-Sastre, A., Lee, S. W., Aaronson, S. A. (2008). Transcriptional role of p53 in interferon-mediated antiviral immunity. JEM 205: 1929-1938 [Abstract] [Full Text]  
  • Chen, M., Lan, S., Ou, R., Price, G. E., Jiang, H., de la Torre, J. C., Moskophidis, D. (2008). Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system. J. Gen. Virol. 89: 1421-1433 [Abstract] [Full Text]  
  • Martinez-Sobrido, L., Giannakas, P., Cubitt, B., Garcia-Sastre, A., de la Torre, J. C. (2007). Differential Inhibition of Type I Interferon Induction by Arenavirus Nucleoproteins. J. Virol. 81: 12696-12703 [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]  
  • Muller, S., Geffers, R., Gunther, S. (2007). Analysis of gene expression in Lassa virus-infected HuH-7 cells. J. Gen. Virol. 88: 1568-1575 [Abstract] [Full Text]  
  • Spiropoulou, C. F., Albarino, C. G., Ksiazek, T. G., Rollin, P. E. (2007). Andes and Prospect Hill Hantaviruses Differ in Early Induction of Interferon although Both Can Downregulate Interferon Signaling. J. Virol. 81: 2769-2776 [Abstract] [Full Text]  
  • Bowick, G. C., Fennewald, S. M., Scott, E. P., Zhang, L., Elsom, B. L., Aronson, J. F., Spratt, H. M., Luxon, B. A., Gorenstein, D. G., Herzog, N. K. (2007). Identification of Differentially Activated Cell-Signaling Networks Associated with Pichinde Virus Pathogenesis by Using Systems Kinomics. J. Virol. 81: 1923-1933 [Abstract] [Full Text]  
  • Kopecky-Bromberg, S. A., Martinez-Sobrido, L., Frieman, M., Baric, R. A., Palese, P. (2007). Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists. J. Virol. 81: 548-557 [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»