Open AccessInhibition of the Type I Interferon Response by the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus
Author(s) -
Luis Martínez-Sobrido,
Elina I. Zúñiga,
Debralee Rosario,
Adolfo Garcı́a-Sastre,
Juan Carlos de la Torre
Publication year - 2006
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00555-06
Subject(s) - arenavirus , lymphocytic choriomeningitis , biology , nucleoprotein , virology , interferon , virus , junin virus , genetics , antigen , cd8
The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is aformidable battle horse for the study of viral immunology, as well asviral persistence and associated diseases. Investigationswith LCMV have uncovered basic mechanisms by which viruses avoidelimination by the host adaptive immune response. In this study we showthat LCMV also disables the host innate defense by interfering withbeta interferon (IFN-β) production in response to differentstimuli, including infection with Sendai virus and liposome-mediatedDNA transfection. Inhibition of IFN production in LCMV-infected cellswas 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 theinhibition of IRF-3 activation. Using expression plasmids encodingindividual LCMV proteins, we found that expression of the LCMVnucleoprotein (NP) was sufficient to inhibit both IFN production andnuclear translocation of IRF-3. To our knowledge, this is the firstevidence of an IFN-counteracting viral protein in theArenaviridae family. Inhibition of IFN production by thearenavirus NP is likely to be a determinant of virulence invivo.