title: West Nile virus encephalitis: sequential histopathological and immunological events in a murine model of infection.
abstract: West Nile virus (WNV) has emerged as an important cause of encephalitis in humans and horses in North America. Although there is significant knowledge about the pathogenesis of disease caused by this flavivirus and about the immunity against it, no reports exist describing the sequence of pathological changes and their correlation to the immune response in the brain following infection with WNV. In this report the authors describe the major histopathological changes, as well as changes in cytokine and chemokine expression, in brains from WNV-infected C57Bl/6 mice. During the course of infection skin, spleen and kidney were all sites of WNV replication before virus reached the brain. In brain, increased expression of the chemokines monocyte chemoattractant protein (MCP)-5 (CCL12), interferon gamma inducible protein 10 (IP-10; CXCL10), and monokine induced by gamma interferon (MIG; CXCL9) preceded the expression of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), which have previously been considered to be key early cytokines in the pathogenesis and immune response of WNV encephalitis. These results suggest that the chemokines MCP-5, IP-10, and MIG are important triggers of inflammation in brain due to their early up-regulation following WNV infection.
authors.affiliation: Department of Veterinary Pathobiology Department, University of Missouri-Columbia, Columbia, Missouri 65211, USA. GarciaTapiaD@missouri.edu
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Tapia
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Hassett
authors.forename: William J
authors.initials: WJ
authors.lastname: Mitchell
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Johnson
authors.forename: Steven B
authors.initials: SB
authors.lastname: Kleiboeker
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019742:Chemokines, CC / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D005260:Female; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis; D013997:Time Factors; D015854:Up-Regulation; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology; D014902:West Nile virus
chemical_list: C491224:Ccl12 protein, mouse; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019742:Chemokines, CC; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; D018945:Monocyte Chemoattractant Proteins; C070959:Ccl6 protein, mouse