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Type: Journal article
Title: Intracranial injection of dengue virus induces interferon stimulated genes and CD8⁺ T cell infiltration by sphingosine kinase 1 independent pathways
Other Titles: Intracranial injection of dengue virus induces interferon stimulated genes and CD8(+) T cell infiltration by sphingosine kinase 1 independent pathways
Author: Al-Shujairi, W.
Clarke, J.
Davies, L.
Alsharifi, M.
Pitson, S.
Carr, J.
Citation: PLoS One, 2017; 12(1):0169814-1-0169814-12
Publisher: Public Library of Science
Issue Date: 2017
ISSN: 1932-6203
Statement of
Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Carr
Abstract: We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.
Keywords: CD4-Positive T-Lymphocytes; Animals; Mice, Inbred C57BL; Mice, Knockout; Mice; Dengue Virus; Dengue; Phosphotransferases (Alcohol Group Acceptor); Interferon-beta; Antiviral Agents; Virus Replication; Gene Expression Regulation; Immunity, Innate
Rights: Copyright: © 2017 Al-Shujairi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030063004
DOI: 10.1371/journal.pone.0169814
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Appears in Collections:Medical Sciences publications

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