Encephalomyocarditis virus induces PKR-independent mitogen-activated protein kinase activation in macrophages. J Virol 2005 Aug;79(16):10226-36
Date
07/30/2005Pubmed ID
16051816Pubmed Central ID
PMC1182679DOI
10.1128/JVI.79.16.10226-10236.2005Scopus ID
2-s2.0-23244467195 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
In this study, we provide evidence that the double-stranded RNA-dependent protein kinase (PKR) is not required for virus-induced expression of inducible nitric oxide synthase (iNOS) or the activation of specific signaling pathways in macrophages. The infection of RAW264.7 cells with encephalomyocarditis virus (EMCV) induces iNOS expression and nitric oxide production, which are unaffected by a dominant-negative mutant of PKR. EMCV infection also activates the mitogen-activated protein kinase, cyclic AMP response element binding protein, and nuclear factor kappaB (NF-kappaB) signaling cascades at 15 to 30 min postinfection in PKR+/+ and PKR-/- macrophages. Activation of these signaling cascades does not temporally correlate with PKR activity or the accumulation of EMCV RNA, suggesting that an interaction between a structural component of the virion and the cell surface may activate macrophages. Consistent with this hypothesis, empty EMCV capsids induced comparable levels of iNOS expression, nitrite production, and activation of these signaling cascades to those induced by intact virions. These findings support the hypothesis that virion-host cell interactions are primary mediators of the PKR-independent activation of signaling pathways that participate in the macrophage antiviral response of inflammatory gene expression.
Author List
Moran JM, Moxley MA, Buller RM, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsEncephalomyocarditis virus
Enzyme Activation
Gene Expression Regulation
Interferon-alpha
MAP Kinase Signaling System
Macrophage Activation
Macrophages
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Transcriptional Activation
Virus Replication
eIF-2 Kinase
