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* Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO 80523;
Department of Biology and Cancer Center, University of California, San Diego, La Jolla, CA 92093;
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;
Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504;
¶ Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520; and
|| Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520
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-
-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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health grant to S.M.H. (AI053091) and a grant to T.W. from Colorado State University. T.T. is supported by an Alzheimer’s Association grant and a National Institutes of Health/National Institute on Aging "Pathway to Independence" award (1K99AG029726-01 and 4R00AG029726). E.F., R.A.F., and T.W. are supported by National Institutes of Health Grants AI055749, AI50031, and AI072060. R.A.F. and E.F. are Investigators of the Howard Hughes Medical Institute.
2 S.W. and T.W. contributed equally to this work.
3 Current address: Departments of Biomedical Sciences and Neurosurgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048.
4 Address correspondence and reprint requests to Dr. Tian Wang, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Campus Delivery 1690, Fort Collins, CO 80523. E-mail address: tian.wang{at}colostate.edu
5 Abbreviations used in this paper: WNV, West Nile virus; BBB, blood brain barrier; EAE, experimental autoimmune encephalomyelitis; i.c., intracranial; Q-PCR, quantitative PCR.
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