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https://hdl.handle.net/2440/81108
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dc.contributor.author | Carr, J. | - |
dc.contributor.author | Kua, T. | - |
dc.contributor.author | Clarke, J. | - |
dc.contributor.author | Calvert, J. | - |
dc.contributor.author | Zebol, J. | - |
dc.contributor.author | Beard, M. | - |
dc.contributor.author | Pitson, S. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Journal of General Virology, 2013; 94(PART 11):2437-2448 | - |
dc.identifier.issn | 0022-1317 | - |
dc.identifier.issn | 1465-2099 | - |
dc.identifier.uri | http://hdl.handle.net/2440/81108 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | J. M. Carr, T. Kua, J. N. Clarke, J. K Calvert, J. R. Zebol, M. R. Beard and S. M. Pitson | - |
dc.language.iso | en | - |
dc.publisher | Soc General Microbiology | - |
dc.rights | © 2013 SGM | - |
dc.source.uri | http://dx.doi.org/10.1099/vir.0.055616-0 | - |
dc.subject | Kidney | - |
dc.subject | Monocytes | - |
dc.subject | Cells, Cultured | - |
dc.subject | Cell Line | - |
dc.subject | Vero Cells | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Dengue Virus | - |
dc.subject | Dengue | - |
dc.subject | Peptide Elongation Factor 1 | - |
dc.subject | Phosphotransferases (Alcohol Group Acceptor) | - |
dc.subject | 3' Untranslated Regions | - |
dc.subject | RNA, Viral | - |
dc.subject | Virus Replication | - |
dc.subject | Apoptosis | - |
dc.subject | Down-Regulation | - |
dc.subject | Cricetinae | - |
dc.subject | HEK293 Cells | - |
dc.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 | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1099/vir.0.055616-0 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1044212 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Beard, M. [0000-0002-4106-1016] | - |
dc.identifier.orcid | Pitson, S. [0000-0002-9527-2740] | - |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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