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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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Copyright © 2006 by the American Society for Microbiology. All rights reserved.