Ccr5 regulates inflammatory gene expression in response to encephalomyocarditis virus infection. Am J Pathol 2011 Dec;179(6):2941-51
Date
10/18/2011Pubmed ID
22001348Pubmed Central ID
PMC3260827DOI
10.1016/j.ajpath.2011.08.012Scopus ID
2-s2.0-81255124282 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Encephalomyocarditis virus (EMCV) is capable of stimulating inflammatory gene expression by macrophages as a result of interactions between EMCV capsid proteins and cell surface receptors. In this study, biochemical and genetic approaches identified a role for Ccr5, a chemokine receptor, in transducing the signals of EMCV infection that result in the expression of inflammatory genes in macrophages. Antibody neutralization and gene knockout strategies were used to show that the presence of Ccr5 is required for EMCV-stimulated mitogen-activated protein (MAP) kinase and nuclear factor-kappa B (NF-κB) activation, and the subsequent expression of the inflammatory gene-inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Ccr5 appears to participate in the early control of virus replication: EMCV mRNA accumulates to sevenfold higher levels in Ccr5-deficient mice when compared to wild-type controls. These findings support a regulatory role for Ccr5 in the antiviral response to EMCV in which this chemokine receptor participates in regulation of inflammatory gene expression in response to virus infection.
Author List
Christmann BS, Moran JM, McGraw JA, 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
AnimalsAntibodies, Neutralizing
Cells, Cultured
Cyclooxygenase 2
DEAD-box RNA Helicases
Encephalomyocarditis virus
Gene Expression
Interferon Type I
Interferon-Induced Helicase, IFIH1
Macrophages
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases
NF-kappa B
Nitric Oxide Synthase Type II
Receptors, CCR5
Signal Transduction
Toll-Like Receptor 3
