title: Drak2 contributes to West Nile virus entry into the brain and lethal encephalitis.
abstract: Death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2), a member of the death-associated protein family of serine/threonine kinases, is specifically expressed in T and B cells. In the absence of Drak2, mice are resistant to experimental autoimmune encephalomyelitis due to a decrease in the number of cells infiltrating the CNS. In the present study, we investigated the role of Drak2 in West Nile virus (WNV)-induced encephalitis and found that Drak2(-/-) mice were also more resistant to lethal WNV infection than wild-type mice. Although Drak2(-/-) mice had an increase in the number of IFN-gamma-producing T cells in the spleen after infection, viral levels in the peripheral tissues were not significantly different between these two groups of mice. In contrast, there was a reduced viral load in the brains of Drak2(-/-) mice, which was accompanied by a decrease in the number of Drak2(-/-) CD4(+) and CD8(+) T cells in the brain following WNV infection. Moreover, we detected viral Ags in T cells isolated from the spleen or brain of WNV-infected mice. These results suggest that following a systemic infection, WNV might cross the blood brain barrier and enter the CNS by being carried by infected infiltrating T cells.
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.forename: Maureen
authors.initials: M
authors.lastname: McGargill
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Jesse
authors.initials: J
authors.lastname: Thompson
authors.forename: John F
authors.initials: JF
authors.lastname: Anderson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hedrick
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D018792:Encephalitis, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D053586:Virus Internalization; D014902:West Nile virus / Q000276:immunology*
chemical_list: D018925:Chemokines; D007371:Interferon-gamma; C495197:Drak2 protein, mouse; D017346:Protein Serine-Threonine Kinases