{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:02:34Z","timestamp":1792440154690,"version":"4.5.0"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SCHN 320\/24-2"],"award-info":[{"award-number":["SCHN 320\/24-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["BE 4080\/3-2"],"award-info":[{"award-number":["BE 4080\/3-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["GRK2581\/1(P3)"],"award-info":[{"award-number":["GRK2581\/1(P3)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism \u2013 as far as they can be tolerated by cells and organisms \u2013 may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach.<\/jats:p>","DOI":"10.3389\/fphys.2021.715527","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T01:17:44Z","timestamp":1632878264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["The Manifold Roles of Sphingolipids in Viral Infections"],"prefix":"10.3389","volume":"12","author":[{"given":"Elita","family":"Avota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Bodem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Chithelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri","family":"Mandasari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Beyersdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Schneider-Schaulies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"324","DOI":"10.3389\/fcell.2019.00324","article-title":"Glycosphingolipids and infection. Potential new therapeutic avenues","volume":"7","author":"Aerts","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"25649","DOI":"10.1074\/jbc.M200554200","article-title":"HIV-1 gp41 envelope residues 650-685 exposed on native virus act as a lectin to bind epithelial cell galactosyl ceramide","volume":"277","author":"Alfsen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"11523","DOI":"10.1128\/JVI.01185-15","article-title":"Cooperation between the hepatitis C virus p7 and NS5B proteins enhances virion infectivity","volume":"89","author":"Aligeti","year":"2015","journal-title":"J. Virol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/nature09128","article-title":"Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2","volume":"465","author":"Alvarez","year":"2010","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"258","DOI":"10.4161\/rna.8.2.15011","article-title":"Hepatitis C virus and host cell lipids: an intimate connection","volume":"8","author":"Alvisi","year":"2011","journal-title":"RNA Biol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"11265","DOI":"10.1074\/jbc.M110.182097","article-title":"Protein kinase D negatively regulates hepatitis C virus secretion through phosphorylation of oxysterol-binding protein and ceramide transfer protein","volume":"286","author":"Amako","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3389\/fmicb.2020.00612","article-title":"Depletion of host and viral sphingomyelin impairs influenza virus infection","volume":"11","author":"Audi","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e1001290","DOI":"10.1371\/journal.ppat.1001290","article-title":"DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells","volume":"7","author":"Avota","year":"2011","journal-title":"PLoS Pathog."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"5676","DOI":"10.3390\/ijms22115676","article-title":"Ceramide and related molecules in viral infections","volume":"22","author":"Beckmann","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/ni.1931","article-title":"SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages","volume":"11","author":"Berger","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.chemphyslip.2018.08.003","article-title":"Sphingolipids and lipid rafts: novel concepts and methods of analysis","volume":"216","author":"Bieberich","year":"2018","journal-title":"Chem. Phys. Lipids"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"6642","DOI":"10.1128\/JVI.00602-16","article-title":"HSP90 chaperoning in addition to phosphoprotein required for folding but not for supporting enzymatic activities of measles and nipah virus L polymerases","volume":"90","author":"Bloyet","year":"2016","journal-title":"J. Virol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.bbamcr.2005.09.001","article-title":"Ceramide-enriched membrane domains","volume":"1746","author":"Bollinger","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"11737","DOI":"10.1128\/JVI.01143-10","article-title":"The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization","volume":"84","author":"Bonsch","year":"2010","journal-title":"J. Virol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"11090","DOI":"10.1073\/pnas.0903535106","article-title":"Structure and assembly of immature HIV","volume":"106","author":"Briggs","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1073\/pnas.0511136103","article-title":"The HIV lipidome: a raft with an unusual composition","volume":"103","author":"Brugger","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e1000621","DOI":"10.1371\/journal.ppat.1000621","article-title":"Virus movements on the plasma membrane support infection and transmission between cells","volume":"5","author":"Burckhardt","year":"2009","journal-title":"PLoS Pathog."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e1005476","DOI":"10.1371\/journal.ppat.1005476","article-title":"Morphology and molecular composition of purified bovine viral diarrhea virus envelope","volume":"12","author":"Callens","year":"2016","journal-title":"PLoS Pathog."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/nature10348","article-title":"Ebola virus entry requires the cholesterol transporter niemann-pick C1","volume":"477","author":"Carette","year":"2011","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.chom.2008.10.013","article-title":"Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis","volume":"4","author":"Carlson","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"100142","DOI":"10.1016\/j.xcrm.2020.100142","article-title":"Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells","volume":"1","author":"Carpinteiro","year":"2020","journal-title":"Cell Rep. Med."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"100701","DOI":"10.1016\/j.jbc.2021.100701","article-title":"Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells","volume":"296","author":"Carpinteiro","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1006\/viro.1994.1287","article-title":"Binding of human immunodeficiency virus type I (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop","volume":"201","author":"Cook","year":"1994","journal-title":"Virology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature10380","article-title":"Small molecule inhibitors reveal niemann-pick C1 is essential for ebola virus infection","volume":"477","author":"Cote","year":"2011","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.3389\/fimmu.2019.01294","article-title":"Measles virus infection fosters dendritic cell motility in a 3D environment to enhance transmission to target cells in the respiratory epithelium","volume":"10","author":"Derakhshani","year":"2019","journal-title":"Front. Immunol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3390\/biom4010315","article-title":"Re-configuration of sphingolipid metabolism by oncogenic transformation","volume":"4","author":"Don","year":"2014","journal-title":"Biomolecules"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"10533","DOI":"10.1128\/JVI.01263-10","article-title":"Primary human mammary epithelial cells endocytose HIV-1 and facilitate viral infection of CD4+ T lymphocytes","volume":"84","author":"Dorosko","year":"2010","journal-title":"J. Virol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e00017","DOI":"10.1128\/JVI.00017-19","article-title":"Glucosylceramidase maintains influenza virus infection by regulating endocytosis","volume":"93","author":"Drews","year":"2019","journal-title":"J. Virol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0228735","DOI":"10.1371\/journal.pone.0228735","article-title":"Glucosylceramide synthase maintains influenza virus entry and infection","volume":"15","author":"Drews","year":"2020","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1159\/000092077","article-title":"Rhinoviral infections activate p38MAP-kinases via membrane rafts and RhoA","volume":"17","author":"Dumitru","year":"2006","journal-title":"Cell. Physiol. Biochem."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"15110","DOI":"10.1073\/pnas.0504407102","article-title":"Single-particle tracking of murine polyoma virus-like particles on live cells and artificial membranes","volume":"102","author":"Ewers","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"105960","DOI":"10.1016\/j.ijantimicag.2020.105960","article-title":"Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection","volume":"55","author":"Fantini","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"eaaw8651","DOI":"10.1126\/sciadv.aaw8651","article-title":"HIV-1 gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly","volume":"5","author":"Favard","year":"2019","journal-title":"Sci. Adv."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1128\/JVI.02553-06","article-title":"Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion","volume":"81","author":"Finnegan","year":"2007","journal-title":"J. Virol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"15452","DOI":"10.1073\/pnas.0402874101","article-title":"Ceramide, a target for antiretroviral therapy","volume":"101","author":"Finnegan","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.mib.2011.07.012","article-title":"Exploitation of cellular pathways by dengue virus","volume":"14","author":"Fischl","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e1000623","DOI":"10.1371\/journal.ppat.1000623","article-title":"Induction of membrane ceramides: a novel strategy to interfere with T lymphocyte cytoskeletal reorganisation in viral immunosuppression","volume":"5","author":"Gassert","year":"2009","journal-title":"PLoS Pathog."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1520.e14","DOI":"10.1016\/j.cell.2020.10.039","article-title":"Beta-coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway","volume":"183","author":"Ghosh","year":"2020","journal-title":"Cell"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"197835","DOI":"10.1016\/j.virusres.2019.197835","article-title":"The role of sphingosine-1-phosphate signaling in HSV-1-infected human umbilical vein endothelial cells","volume":"276","author":"Graber","year":"2020","journal-title":"Virus Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3389\/fcell.2019.00218","article-title":"Use of acid ceramidase and sphingosine kinase inhibitors as antiviral compounds against measles virus infection of lymphocytes in vitro","volume":"7","author":"Grafen","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.plipres.2007.03.002","article-title":"Biological aspects of ceramide-enriched membrane domains","volume":"46","author":"Grassme","year":"2007","journal-title":"Prog. Lipid Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00109-004-0539-y","article-title":"Ceramide, membrane rafts and infections","volume":"82","author":"Gulbins","year":"2004","journal-title":"J. Mol. Med."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/s1388-1981(02)00334-7","article-title":"Ceramide and cell death receptor clustering","volume":"1585","author":"Gulbins","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"7967","DOI":"10.1074\/jbc.273.14.7967","article-title":"Specific interaction of HIV-1 and HIV-2 surface envelope glycoproteins with monolayers of galactosylceramide and ganglioside GM3","volume":"273","author":"Hammache","year":"","journal-title":"J. Biol. Chem."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1006\/bbrc.1998.8531","article-title":"Sequential interaction of CD4 and HIV-1 gp120 with a reconstituted membrane patch of ganglioside GM3: implications for the role of glycolipids as potential HIV-1 fusion cofactors","volume":"246","author":"Hammache","year":"","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s10719-010-9297-y","article-title":"A synthetic globotriaosylceramide analogue inhibits HIV-1 infection in vitro by two mechanisms","volume":"27","author":"Harrison","year":"2010","journal-title":"Glycoconj. J."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"30842","DOI":"10.1074\/jbc.M114.574285","article-title":"Sphingomyelin synthase 2, but not sphingomyelin synthase 1, is involved in HIV-1 envelope-mediated membrane fusion","volume":"289","author":"Hayashi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"271.e8","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/S0006-3495(00)76640-9","article-title":"Vectorial budding of vesicles by asymmetrical enzymatic formation of ceramide in giant liposomes","volume":"78","author":"Holopainen","year":"2000","journal-title":"Biophys. J."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"102266","DOI":"10.1016\/j.isci.2021.102266","article-title":"The sphingosine kinase 1 activator, K6PC-5, attenuates ebola virus infection","volume":"24","author":"Imre","year":"2021","journal-title":"iScience"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"12276","DOI":"10.1128\/JVI.00970-14","article-title":"Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2","volume":"88","author":"Khan","year":"2014","journal-title":"J. Virol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"e23852","DOI":"10.1371\/journal.pone.0023852","article-title":"Identification of novel functional inhibitors of acid sphingomyelinase","volume":"6","author":"Kornhuber","year":"2011","journal-title":"PLoS One"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tips.2014.04.003","article-title":"The ceramide system as a novel antidepressant target","volume":"35","author":"Kornhuber","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"9880","DOI":"10.1128\/JVI.00909-08","article-title":"NF-kappaB signaling differentially regulates influenza virus RNA synthesis","volume":"82","author":"Kumar","year":"2008","journal-title":"J. Virol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1038\/s41467-020-15072-8","article-title":"Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease","volume":"11","author":"Lang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1083\/jcb.200503059","article-title":"Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells","volume":"170","author":"Lehmann","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1038\/s41467-020-17433-9","article-title":"A global lipid map defines a network essential for zika virus replication","volume":"11","author":"Leier","year":"2020","journal-title":"Nat. Commun."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.chemphyslip.2009.09.001","article-title":"New aspects of the regulation of glycosphingolipid receptor function","volume":"163","author":"Lingwood","year":"2010","journal-title":"Chem. Phys. Lipids"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1111\/cmi.12101","article-title":"Comparative lipidomics analysis of HIV-1 particles and their producer cell membrane in different cell lines","volume":"15","author":"Lorizate","year":"2013","journal-title":"Cell Microbiol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.chom.2015.06.006","article-title":"Co-option of membrane wounding enables virus penetration into cells","volume":"18","author":"Luisoni","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1097\/01.aids.0000183521.90878.79","article-title":"Lack of susceptibility of cells from patients with fabry disease to productive infection with R5 human immunodeficiency virus","volume":"19","author":"Lund","year":"2005","journal-title":"AIDS"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"4980","DOI":"10.1182\/blood-2008-03-143396","article-title":"The human P(k) histo-blood group antigen provides protection against HIV-1 infection","volume":"113","author":"Lund","year":"2009","journal-title":"Blood"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e00297","DOI":"10.1128\/mBio.00297-16","article-title":"Interaction between simian virus 40 major capsid protein VP1 and cell surface ganglioside GM1 triggers vacuole formation","volume":"7","author":"Luo","year":"2016","journal-title":"mBio"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.virol.2006.11.035","article-title":"Galactosyl ceramide expressed on dendritic cells can mediate HIV-1 transfer from monocyte derived dendritic cells to autologous T cells","volume":"362","author":"Magerus-Chatinet","year":"2007","journal-title":"Virology"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1194\/jlr.M064212","article-title":"Host sphingomyelin increases West Nile virus infection in vivo","volume":"57","author":"Martin-Acebes","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1126\/science.1155164","article-title":"Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells","volume":"320","author":"Mercer","year":"2008","journal-title":"Science"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/ncb0509-510","article-title":"Virus entry by macropinocytosis","volume":"11","author":"Mercer","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1038\/emboj.2012.53","article-title":"Ebola virus entry requires the host-programmed recognition of an intracellular receptor","volume":"31","author":"Miller","year":"","journal-title":"EMBO J."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"7473","DOI":"10.1128\/JVI.00136-12","article-title":"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection","volume":"86","author":"Miller","year":"","journal-title":"J. Virol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1128\/AEM.00275-16","article-title":"Wolbachia modulates lipid metabolism in aedes albopictus mosquito cells","volume":"82","author":"Molloy","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1165\/rcmb.2003-0424OC","article-title":"Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus","volume":"30","author":"Monick","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"8360","DOI":"10.1128\/JVI.00443-10","article-title":"Virus cell-to-cell transmission","volume":"84","author":"Mothes","year":"2010","journal-title":"J. Virol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"e1004574","DOI":"10.1371\/journal.ppat.1004574","article-title":"Neutral sphingomyelinase in physiological and measles virus induced T cell suppression","volume":"10","author":"Mueller","year":"2014","journal-title":"PLoS Pathog."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3390\/molecules24030481","article-title":"A spotlight on viruses-application of click chemistry to visualize virus-cell interactions","volume":"24","author":"Muller","year":"2019","journal-title":"Molecules"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"e01836","DOI":"10.1128\/mBio.01836-16","article-title":"Murine polyomavirus cell surface receptors activate distinct signaling pathways required for infection","volume":"7","author":"O\u2019Hara","year":"2016","journal-title":"mBio"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/s41564-018-0221-8","article-title":"Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection","volume":"3","author":"Orchard","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e01130","DOI":"10.1128\/JVI.01130-17","article-title":"Both sphingomyelin and cholesterol in the host cell membrane are essential for rubella virus entry","volume":"92","author":"Otsuki","year":"2018","journal-title":"J. Virol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e01547","DOI":"10.1128\/JVI.01547-18","article-title":"Role of sphingomyelin in alphaherpesvirus entry","volume":"93","author":"Pastenkos","year":"2019","journal-title":"J. Virol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"e106272","DOI":"10.15252\/embj.2020106272","article-title":"Cellular stress promotes NOD1\/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate","volume":"40","author":"Pei","year":"2021","journal-title":"EMBO J."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/j.bbamem.2012.02.010","article-title":"Ceramide channels: influence of molecular structure on channel formation in membranes","volume":"1818","author":"Perera","year":"","journal-title":"Biochim. Biophys. Acta"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"e1002584","DOI":"10.1371\/journal.ppat.1002584","article-title":"Dengue virus infection perturbs lipid homeostasis in infected mosquito cells","volume":"8","author":"Perera","year":"","journal-title":"PLoS Pathog."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1038\/s41564-019-0453-2","article-title":"Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry","volume":"4","author":"Perez-Zsolt","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1097\/00002030-200404090-00002","article-title":"An inhibitor of glycosphingolipid metabolism blocks HIV-1 infection of primary T-cells","volume":"18","author":"Puri","year":"2004","journal-title":"AIDS"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e1003291","DOI":"10.1371\/journal.ppat.1003291","article-title":"Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1\/CD169","volume":"9","author":"Puryear","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1093\/glycob\/cwn106","article-title":"Induction of HIV-1 resistance: cell susceptibility to infection is an inverse function of globotriaosyl ceramide levels","volume":"19","author":"Ramkumar","year":"2009","journal-title":"Glycobiology"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"7360","DOI":"10.1128\/JVI.78.14.7360-7368.2004","article-title":"Elevated expression of GM3 in receptor-bearing targets confers resistance to human immunodeficiency virus type 1 fusion","volume":"78","author":"Rawat","year":"2004","journal-title":"J. Virol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1080\/09687680701613713","article-title":"Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion","volume":"25","author":"Rawat","year":"2008","journal-title":"Mol. Membr. Biol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1038\/emi.2015.61","article-title":"Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex","volume":"4","author":"Reid","year":"2015","journal-title":"Emerg. Microbes Infect."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e1000148","DOI":"10.1371\/journal.ppat.1000148","article-title":"Human papillomavirus type 16 entry: retrograde cell surface transport along actin-rich protrusions","volume":"4","author":"Schelhaas","year":"2008","journal-title":"PLoS Pathog."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1080\/22221751.2020.1829082","article-title":"Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine","volume":"9","author":"Schloer","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1515\/hsz-2014-0273","article-title":"Sphingolipids in viral infection","volume":"396","author":"Schneider-Schaulies","year":"2015","journal-title":"Biol. Chem."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"745","DOI":"10.3390\/v12070745","article-title":"Revisiting membrane microdomains and phase separation: a viral perspective","volume":"12","author":"Sengupta","year":"2020","journal-title":"Viruses"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s41556-019-0300-y","article-title":"A lipid-based partitioning mechanism for selective incorporation of proteins into membranes of HIV particles","volume":"21","author":"Sengupta","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"8124","DOI":"10.1128\/JVI.00510-10","article-title":"Sphingosine 1-phosphate-metabolizing enzymes control influenza virus propagation and viral cytopathogenicity","volume":"84","author":"Seo","year":"2010","journal-title":"J. Virol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"e75005","DOI":"10.1371\/journal.pone.0075005","article-title":"Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA synthesis and nuclear export of viral ribonucleoprotein complex upon influenza virus infection","volume":"8","author":"Seo","year":"2013","journal-title":"PLoS One"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ncb1544","article-title":"Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission","volume":"9","author":"Sherer","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"e00053","DOI":"10.1128\/JVI.00053-19","article-title":"Ceramide suppresses influenza A virus replication in vitro","volume":"93","author":"Soudani","year":"2019","journal-title":"J. Virol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ceb.2017.02.005","article-title":"Viral rewiring of cellular lipid metabolism to create membranous replication compartments","volume":"47","author":"Strating","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"6523","DOI":"10.1172\/JCI125297","article-title":"Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence","volume":"130","author":"Studstill","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1128\/JVI.02499-09","article-title":"Involvement of ceramide in the propagation of Japanese encephalitis virus","volume":"84","author":"Tani","year":"2010","journal-title":"J. Virol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"37829","DOI":"10.1038\/srep37829","article-title":"Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and infection with Japanese encephalitis virus","volume":"6","author":"Taniguchi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/jmv.21970","article-title":"Host sphingolipid biosynthesis is a promising therapeutic target for the inhibition of hepatitis B virus replication","volume":"83","author":"Tatematsu","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"e00835","DOI":"10.1128\/JVI.00835-18","article-title":"APOBEC3G-regulated host factors interfere with measles virus replication: role of REDD1 and mammalian TORC1 inhibition","volume":"92","author":"Tiwarekar","year":"2018","journal-title":"J. Virol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"689854","DOI":"10.3389\/fcell.2021.689854","article-title":"Sphingolipids as modulators of SARS-CoV-2 infection","volume":"9","author":"Tornquist","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"793815","DOI":"10.1155\/2014\/793815","article-title":"Influenza viral manipulation of sphingolipid metabolism and signaling to modulate host defense system","volume":"2014","author":"Vijayan","year":"2014","journal-title":"For. Sci."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.virol.2013.11.039","article-title":"Sphingosine kinase 1 regulates measles virus replication","author":"Vijayan","year":"2014","journal-title":"Virology"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/j.1462-5822.2007.01070.x","article-title":"Ceramide enrichment of the plasma membrane induces CD81 internalization and inhibits hepatitis C virus entry","volume":"10","author":"Voisset","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"e00127","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J. Virol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.2174\/0929867326666190308133732","article-title":"FTY720 (Fingolimod) ameliorates brain injury through multiple mechanisms and is a strong candidate for stroke treatment","volume":"27","author":"Wang","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"11761","DOI":"10.1128\/JVI.00638-10","article-title":"Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner","volume":"84","author":"Weng","year":"2010","journal-title":"J. Virol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.3390\/v11121097","article-title":"Emerging connections of S1P-metabolizing enzymes with host defense and immunity during virus infections","volume":"11","author":"Wolf","year":"2019","journal-title":"Viruses"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"13648","DOI":"10.1074\/jbc.M807498200","article-title":"Inhibition of sphingosine kinase by bovine viral diarrhea virus NS3 is crucial for efficient viral replication and cytopathogenesis","volume":"284","author":"Yamane","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ceca.2007.04.011","article-title":"The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor, galactosyl ceramide, is structure-dependent","volume":"43","author":"Yu","year":"2008","journal-title":"Cell Calcium"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1083\/jcb.200705060","article-title":"Remodeling of cellular cytoskeleton by the acid sphingomyelinase\/ceramide pathway","volume":"181","author":"Zeidan","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1083\/jcb.140.1.39","article-title":"Sphingomyelinase treatment induces ATP-independent endocytosis","volume":"140","author":"Zha","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fmicb.2019.00286","article-title":"Host lipids in positive-strand RNA virus genome replication","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00430-018-0543-4","article-title":"Influence of sphingosine-1-phosphate signaling on HCMV replication in human embryonal lung fibroblasts","volume":"207","author":"Zilch","year":"2018","journal-title":"Med. Microbiol. Immunol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"5890","DOI":"10.1038\/s41598-021-85049-0","article-title":"The serotonin reuptake inhibitor fluoxetine inhibits SARS-CoV-2 in human lung tissue","volume":"11","author":"Zimniak","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.715527\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T01:17:47Z","timestamp":1632878267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.715527\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":119,"alternative-id":["10.3389\/fphys.2021.715527"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.715527","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]},"article-number":"715527"}}