{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:19Z","timestamp":1792789639723,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000735","name":"University of Cambridge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT100321\/z\/12\/Z"],"award-info":[{"award-number":["WT100321\/z\/12\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.celrep.2022.111562","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T11:15:12Z","timestamp":1666696512000},"page":"111562","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activation of Toll-like receptor 4 by Ebola virus-shed glycoprotein is direct and requires the internal fusion loop but not glycosylation"],"prefix":"10.1016","volume":"41","author":[{"given":"Michael J.","family":"Scherm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Gangloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-7169","authenticated-orcid":false,"given":"Nicholas J.","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2022.111562_bib1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1247749","article-title":"Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system","volume":"343","author":"Akey","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.celrep.2022.111562_bib2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-pathol-052016-100506","article-title":"The pathogenesis of ebola virus disease","volume":"12","author":"Baseler","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.celrep.2022.111562_bib3","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1093\/infdis\/jiw207","article-title":"Discovery and description of ebola Zaire virus in 1976 and relevance to the west African epidemic during 2013-2016","volume":"214","author":"Breman","year":"2016","journal-title":"J.\u00a0Infect. Dis."},{"key":"10.1016\/j.celrep.2022.111562_bib4","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3109\/10409238.2015.1033511","article-title":"Advances in Toll-like receptor biology: modes of activation by diverse stimuli","volume":"50","author":"Bryant","year":"2015","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"10.1016\/j.celrep.2022.111562_bib5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/nrmicro2266","article-title":"The molecular basis of the host response to lipopolysaccharide","volume":"8","author":"Bryant","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.celrep.2022.111562_bib6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/prot.10389","article-title":"ZDOCK: an initial-stage protein-docking algorithm","volume":"52","author":"Chen","year":"2003","journal-title":"Proteins"},{"key":"10.1016\/j.celrep.2022.111562_bib7","doi-asserted-by":"crossref","first-page":"10982","DOI":"10.1128\/JVI.01490-15","article-title":"Mechanism of binding to ebola virus glycoprotein by the ZMapp, ZMAb, and MB-003 cocktail antibodies","volume":"89","author":"Davidson","year":"2015","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.celrep.2022.111562_bib8","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/sj.emboj.7600219","article-title":"Ectodomain shedding of the glycoprotein GP of Ebola virus","volume":"23","author":"Dolnik","year":"2004","journal-title":"EMBO J."},{"key":"10.1016\/j.celrep.2022.111562_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004509","article-title":"Shed GP of ebola virus triggers immune activation and increased vascular permeability","volume":"10","author":"Escudero-P\u00e9rez","year":"2014","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2022.111562_bib10","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/cdd.2015.67","article-title":"Molecular mechanisms of Ebola virus pathogenesis: focus on cell death","volume":"22","author":"Falasca","year":"2015","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.celrep.2022.111562_bib11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-3-7091-9300-6_8","article-title":"Molecular biology and evolution of filoviruses","volume":"7","author":"Feldmann","year":"1993","journal-title":"Arch. Virol. Suppl."},{"key":"10.1016\/j.celrep.2022.111562_bib12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1006\/viro.1994.1147","article-title":"Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein","volume":"199","author":"Feldmann","year":"1994","journal-title":"Virology"},{"key":"10.1016\/j.celrep.2022.111562_bib13","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-23357-8","article-title":"A critical domain of ebolavirus envelope glycoprotein determines glycoform and infectivity","volume":"8","author":"Fujihira","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2022.111562_bib14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3109\/10409231003628015","article-title":"ADAM-17: the enzyme that does it all","volume":"45","author":"Gooz","year":"2010","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"10.1016\/j.celrep.2022.111562_bib15","doi-asserted-by":"crossref","first-page":"11211","DOI":"10.1073\/pnas.1104760108","article-title":"Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2","volume":"108","author":"Gregory","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2022.111562_bib16","first-page":"310","article-title":"Prediction of glycosylation across the human proteome and the correlation to protein function","author":"Gupta","year":"2002","journal-title":"Pac. Symp. Biocomput."},{"key":"10.1016\/j.celrep.2022.111562_bib17","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fcimb.2020.00048","article-title":"N-glycans mediate the ebola virus-GP1 shielding of ligands to immune receptors and immune evasion","volume":"10","author":"Iraqi","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.celrep.2022.111562_bib18","doi-asserted-by":"crossref","first-page":"12463","DOI":"10.1128\/JVI.76.24.12463-12472.2002","article-title":"Covalent modifications of the ebola virus glycoprotein","volume":"76","author":"Jeffers","year":"2002","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.celrep.2022.111562_bib19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature07082","article-title":"Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor","volume":"454","author":"Lee","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2022.111562_bib20","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2217\/fvl.09.56","article-title":"Ebolavirus glycoprotein structure and mechanism of entry","volume":"4","author":"Lee","year":"2009","journal-title":"Future Virol."},{"key":"10.1016\/j.celrep.2022.111562_bib21","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13054-016-1325-2","article-title":"Ebola virus disease and critical illness","volume":"20","author":"Leligdowicz","year":"2016","journal-title":"Crit. Care"},{"key":"10.1016\/j.celrep.2022.111562_bib22","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/438575a","article-title":"Fruit bats as reservoirs of Ebola virus","volume":"438","author":"Leroy","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2022.111562_bib23","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1007\/s00018-015-1915-1","article-title":"Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface","volume":"72","author":"Lonez","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.celrep.2022.111562_bib24","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2005860","article-title":"Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles","volume":"8","author":"Man\u010dek-Keber","year":"2015","journal-title":"Sci. Signal."},{"key":"10.1016\/j.celrep.2022.111562_bib25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/mol.110.068064","article-title":"TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules","volume":"79","author":"Matsunaga","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.celrep.2022.111562_bib26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.cell.2014.10.006","article-title":"Camouflage and misdirection: the full-on assault of ebola virus disease","volume":"159","author":"Misasi","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2022.111562_bib27","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aad8657","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity","volume":"7","author":"Stacey","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.celrep.2022.111562_bib28","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/9673537","article-title":"Recent advances in ADAM17 research: a promising target for cancer and inflammation","volume":"2017","author":"Moss","year":"2017","journal-title":"Mediators Inflamm."},{"key":"10.1016\/j.celrep.2022.111562_bib29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1128\/JVI.01462-09","article-title":"Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1","volume":"84","author":"Okumura","year":"2010","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.celrep.2022.111562_bib30","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00179-17","article-title":"Ebolaviruses associated with differential pathogenicity induce distinct host responses in human macrophages","volume":"91","author":"Olejnik","year":"2017","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.celrep.2022.111562_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007390","article-title":"Toll-like receptor 4 in acute viral infection: too much of a good thing","volume":"14","author":"Olejnik","year":"2018","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2022.111562_bib32","doi-asserted-by":"crossref","DOI":"10.1038\/srep23743","article-title":"Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses","volume":"6","author":"Pappalardo","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2022.111562_bib33","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/nature07830","article-title":"The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex","volume":"458","author":"Park","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2022.111562_bib34","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.celrep.2022.111562_bib35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0024657","article-title":"Accelerating protein docking in ZDOCK using an advanced 3D convolution library","volume":"6","author":"Pierce","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2022.111562_bib36","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1007\/s00018-019-03113-5","article-title":"Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4","volume":"76","author":"Pizzuto","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.celrep.2022.111562_bib37","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.micinf.2005.04.006","article-title":"The natural history of Ebola virus in Africa","volume":"7","author":"Pourrut","year":"2005","journal-title":"Microbes Infect."},{"key":"10.1016\/j.celrep.2022.111562_bib38","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1074\/jbc.M609400200","article-title":"Specific high affinity interactions of monomeric Endotoxin{middle dot}Protein complexes with toll-like receptor 4 ectodomain","volume":"282","author":"Prohinar","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.celrep.2022.111562_bib39","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/embor.2012.155","article-title":"Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2","volume":"13","author":"Raghavan","year":"2012","journal-title":"EMBO Rep."},{"key":"10.1016\/j.celrep.2022.111562_bib40","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1016\/j.celrep.2020.03.025","article-title":"Structure-based design of prefusion-stabilized filovirus glycoprotein trimers","volume":"30","author":"Rutten","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2022.111562_bib41","doi-asserted-by":"crossref","first-page":"W310","DOI":"10.1093\/nar\/gkl206","article-title":"GRAMM-X public web server for protein-protein docking","volume":"34","author":"Tovchigrechko","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2022.111562_bib42","doi-asserted-by":"crossref","first-page":"5762","DOI":"10.1073\/pnas.95.10.5762","article-title":"Processing of the Ebola virus glycoprotein by the proprotein convertase furin","volume":"95","author":"Volchkov","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2022.111562_bib43","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1074\/jbc.M116.768168","article-title":"Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function","volume":"292","author":"Wang","year":"2017","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.celrep.2022.111562_bib44","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cell.2015.12.044","article-title":"Ebola viral glycoprotein bound to its endosomal receptor niemann-pick C1","volume":"164","author":"Wang","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2022.111562_bib45","first-page":"E884","article-title":"TLR4\/MD-2 activation by a synthetic agonist with no similarity to LPS","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2022.111562_bib46","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S1097-2765(00)80159-8","article-title":"Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain","volume":"2","author":"Weissenhorn","year":"1998","journal-title":"Mol. Cell"},{"key":"10.1016\/j.celrep.2022.111562_bib47","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein-protein docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.celrep.2022.111562_bib48","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00226-17","article-title":"The toll-like receptor 4 antagonist eritoran protects mice from lethal filovirus challenge","volume":"8","author":"Younan","year":"2017","journal-title":"mBio"},{"key":"10.1016\/j.celrep.2022.111562_bib49","doi-asserted-by":"crossref","first-page":"27916","DOI":"10.1074\/jbc.M802826200","article-title":"Paclitaxel binding to human and murine MD-2","volume":"283","author":"Zimmer","year":"2008","journal-title":"J.\u00a0Biol. Chem."}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124722014231?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124722014231?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:50:58Z","timestamp":1778842258000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124722014231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["S2211124722014231"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2022.111562","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Activation of Toll-like receptor 4 by Ebola virus-shed glycoprotein is direct and requires the internal fusion loop but not glycosylation","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2022.111562","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s).","name":"copyright","label":"Copyright"}],"article-number":"111562"}}