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https://hdl.handle.net/2440/81108
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Type: | Journal article |
Title: | Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3' untranslated region of dengue virus type-2 RNA |
Author: | Carr, J. Kua, T. Clarke, J. Calvert, J. Zebol, J. Beard, M. Pitson, S. |
Citation: | Journal of General Virology, 2013; 94(PART 11):2437-2448 |
Publisher: | Soc General Microbiology |
Issue Date: | 2013 |
ISSN: | 0022-1317 1465-2099 |
Statement of Responsibility: | J. M. Carr, T. Kua, J. N. Clarke, J. K Calvert, J. R. Zebol, M. R. Beard and S. M. Pitson |
Abstract: | Sphingosine kinase 1 (SphK1) is a lipid kinase with important roles including regulation of cell survival. We have previously shown reduced SphK1 activity in cells with an established dengue virus type-2 (DENV-2) infection. In this study, we examined the effect of alterations in SphK1 activity on DENV-2 replication and cell death and determined the mechanisms of the reduction in SphK1 activity. Chemical inhibition or overexpression of SphK1 after established DENV-2 infection had no effect on infectious DENV-2 production, although inhibition of SphK1 resulted in enhanced DENV-2-induced cell death. Reduced SphK1 activity was observed in multiple cell types, regardless of the ability of DENV-2 infection to be cytopathic, and was mediated by a post-translational mechanism. Unlike bovine viral diarrhea virus, where SphK1 activity is decreased by the NS3 protein, SphK1 activity was not affected by DENV-2 NS3 but, instead, was reduced by expression of the terminal 396 bases of the 3' UTR of DENV-2 RNA. We have previously shown that eukaryotic elongation factor 1A (eEF1A) is a direct activator of SphK1 and here DENV-2 RNA co-localized and co-precipitated with eEF1A from infected cells. We propose that the reduction in SphK1 activity late in DENV-2-infected cells is a consequence of DENV-2 out-competing SphK1 for eEF1A binding and hijacking cellular eEF1A for its own replication strategy, rather than a specific host or virus-induced change in SphK1 to modulate viral replication. Nonetheless, reduced SphK1 activity may have important consequences for survival or death of the infected cell. |
Keywords: | Kidney Monocytes Cells, Cultured Cell Line Vero Cells Animals Humans Dengue Virus Dengue Peptide Elongation Factor 1 Phosphotransferases (Alcohol Group Acceptor) 3' Untranslated Regions RNA, Viral Virus Replication Apoptosis Down-Regulation Cricetinae HEK293 Cells |
Rights: | © 2013 SGM |
DOI: | 10.1099/vir.0.055616-0 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1044212 |
Published version: | http://dx.doi.org/10.1099/vir.0.055616-0 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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