Drak2 contributes to West Nile virus entry into the brain and lethal encephalitis.
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.
Wang
Shuhui
S
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Welte
Thomas
T
McGargill
Maureen
M
Town
Terrence
T
Thompson
Jesse
J
Anderson
John F
JF
Flavell
Richard A
RA
Fikrig
Erol
E
Hedrick
Stephen M
SM
Wang
Tian
T
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*
D018925:Chemokines; D007371:Interferon-gamma; C495197:Drak2 protein, mouse; D017346:Protein Serine-Threonine Kinases