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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.




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