title: Ccr5 regulates inflammatory gene expression in response to encephalomyocarditis virus infection.
abstract: 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.
authors: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA.
authors: Benjamin S
authors: BS
authors: Christmann
authors: Jason M
authors: JM
authors: Moran
authors: Jennifer A
authors: JA
authors: McGraw
authors: R Mark L
authors: RM
authors: Buller
authors: John A
authors: JA
authors: Corbett
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000502:physiology; D004686:Encephalomyocarditis virus / Q000502:physiology*; D015870:Gene Expression; D007370:Interferon Type I / Q000096:biosynthesis*; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019713:Receptors, CCR5 / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; D007370:Interferon Type I; D016328:NF-kappa B; D019713:Receptors, CCR5; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1