{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:09:26Z","timestamp":1791202166506,"version":"4.2.0"},"reference-count":120,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,5,28]],"date-time":"2012-05-28T00:00:00Z","timestamp":1338163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reviews in Medical Virology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Sphingosine kinase 1 (SphK1) is an enzyme that phosphorylates the lipid sphingosine to generate sphingosine\u20101\u2010phosphate (S1P). S1P can act intracellularly as a signaling molecule and extracellularly as a receptor ligand. The SphK1\/S1P axis has well\u2010described roles in cell signaling, the cell death\/survival decision, the production of a pro\u2010inflammatory response, immunomodulation, and control of vascular integrity. Agents targeting the SphK1\/S1P axis are being actively developed as therapeutics for cancer and immunological and inflammatory disorders. Control of cell death\/survival and pro\u2010inflammatory immune responses is central to the pathology of infectious disease, and we can capitalize on the knowledge provided by investigations of SphK1\/S1P in cancer and immunology to assess its application to selected human infections. We have herein reviewed the growing literature relating viral infections to changes in SphK1 and S1P. SphK1 activity is reportedly increased following human cytomegalovirus and respiratory syncytial virus infections, and elevated SphK1 enhances influenza virus infection. In contrast, SphK1 activity is reduced in bovine viral diarrhea virus and dengue virus infections. Sphingosine analogs that modulate S1P receptors have proven useful in animal models in alleviating influenza virus infection but have shown no benefit in simian human immunodeficiency virus and lymphocytic choriomeningitis virus infections. We have rationalized a role for SphK1\/S1P in dengue virus, chikungunya virus, and Ross River virus infections, on the basis of the biology and the pathology of these diseases. The increasing number of effective SphK1 and S1P modulating agents currently in development makes it timely to investigate these roles with the potential for developing modulators of SphK1 and S1P for novel anti\u2010viral therapies. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/rmv.1718","type":"journal-article","created":{"date-parts":[[2012,5,28]],"date-time":"2012-05-28T09:09:19Z","timestamp":1338196159000},"page":"73-84","source":"Crossref","is-referenced-by-count":49,"title":["Sphingosine kinase 1 in viral infections"],"prefix":"10.1002","volume":"23","author":[{"given":"Jillian M.","family":"Carr","sequence":"first","affiliation":[{"name":"Microbiology and Infectious Diseases, Flinders Medical Science and Technology, School of Medicine Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Mahalingam","sequence":"additional","affiliation":[{"name":"Institute for Glycomics Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine S.","family":"Bonder","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Pitson","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2329"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800065-JLR200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.107.07113"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.072407.103733"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800910791208599"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2364"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.08.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2010.09.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2974"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2400"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advenzreg.2010.09.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2011.580097"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-6741-1_10"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540600871126"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/381800a0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg540"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804658200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.11.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.068395"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.420"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M004374"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20967"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-8831-5_10"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2006.09.026"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00331-1"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.04.004"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111423200"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09128"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708895200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00510-10"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2010.12.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.91"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/S0021-9258(18)52461-3","article-title":"Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma\u2010interferon. Specific role in cell differentiation","volume":"266","author":"Kim MY","year":"1991","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8456305"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902926"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21101"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139221"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22507"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(01)00103-4"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.165845"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1650"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.11.002"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1545"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939858"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2047"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.1596"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.2960"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-362574"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1523"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603734103"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-115451"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.2217\/17460875.3.6.665"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030680"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803430"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.06.003"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506182200"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.2811"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3551"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.24.11113-11121.2005"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1586"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-166942"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20193"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14196"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091016"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090076"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-092148"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176709"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio804"},{"key":"e_1_2_9_70_1","first-page":"1871","article-title":"Sphingosine\u20101\u2010phosphate in the plasma compartment regulates basal and inflammation\u2010induced vascular leak in mice","volume":"119","author":"Camerer E","year":"2009","journal-title":"The Journal of Clinical Investigation"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.199778"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02397-07"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.10340"},{"key":"e_1_2_9_74_1","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1128\/jvi.71.6.4226-4232.1997","article-title":"Activation of endothelial cells via antibody\u2010enhanced dengue virus infection of peripheral blood monocytes","volume":"71","author":"Anderson R","year":"1997","journal-title":"Journal of Virology"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21408"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906467106"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.028159-0"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010657"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01140-09"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.045989-0"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(76)90053-9"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(91)90049-4"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00144-10"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.04.007"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01292-06"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.10.076"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.01046.x"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02020-09"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0424OC"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710181200"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807498200"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610581200"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3248"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm101183p"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812689106"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107024108"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.015"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.06.132"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-011-8240-z"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp008"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.08.043"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00035-09"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3014"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70166-3"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2009.80.416"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1086\/383043"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101089108"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1086\/587841"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001279"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir470"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24682"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000130537.76808.26"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.2478\/s11658-009-0009-1"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21668"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8010"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2009.02381.x"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4323"},{"key":"e_1_2_9_119_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000644"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.07.035"},{"key":"e_1_2_9_121_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945011795677836"}],"container-title":["Reviews in Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Frmv.1718","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.1718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T05:49:49Z","timestamp":1700632189000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmv.1718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,28]]},"references-count":120,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/rmv.1718"],"URL":"https:\/\/doi.org\/10.1002\/rmv.1718","archive":["Portico"],"relation":{},"ISSN":["1052-9276","1099-1654"],"issn-type":[{"value":"1052-9276","type":"print"},{"value":"1099-1654","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,28]]}}}