Document Detail


Drak2 contributes to West Nile virus entry into the brain and lethal encephalitis.
MedLine Citation:
PMID:  18641347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Shuhui Wang; Thomas Welte; Maureen McGargill; Terrence Town; Jesse Thompson; John F Anderson; Richard A Flavell; Erol Fikrig; Stephen M Hedrick; Tian Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-08-19     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2084-91     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Movement / immunology
Cells, Cultured
Chemokines / immunology,  metabolism
Encephalitis, Viral / genetics,  immunology*,  metabolism*,  virology
Female
Interferon-gamma / biosynthesis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein-Serine-Threonine Kinases / deficiency,  genetics,  metabolism*
Spleen / immunology,  metabolism
Survival Rate
T-Lymphocytes / cytology,  immunology
Virus Internalization*
West Nile virus / immunology*
Grant Support
ID/Acronym/Agency:
1K99AG029726-01/AG/NIA NIH HHS; 4R00AG029726/AG/NIA NIH HHS; AI053091/AI/NIAID NIH HHS; AI055749/AI/NIAID NIH HHS; AI072060/AI/NIAID NIH HHS; AI50031/AI/NIAID NIH HHS; K99 AG029726/AG/NIA NIH HHS; K99 AG029726-01/AG/NIA NIH HHS; R00 AG029726/AG/NIA NIH HHS; R00 AG029726-02/AG/NIA NIH HHS; R01 AI032947/AI/NIAID NIH HHS; R01 AI041440/AI/NIAID NIH HHS; R01 AI053091/AI/NIAID NIH HHS; R01 AI053091-05/AI/NIAID NIH HHS; R01 AI055749/AI/NIAID NIH HHS; R01 AI055749-05/AI/NIAID NIH HHS; R01 AI072060/AI/NIAID NIH HHS; R01 AI072060-01A2/AI/NIAID NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Chemokines; 82115-62-6/Interferon-gamma; EC 2.7.11.1/Drak2 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

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