{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:56:52Z","timestamp":1790474212135,"version":"4.1.0"},"reference-count":105,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":200,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI095436"],"award-info":[{"award-number":["R01 AI095436"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI142790"],"award-info":[{"award-number":["U19 AI142790"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI007172"],"award-info":[{"award-number":["T32 AI007172"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL069765"],"award-info":[{"award-number":["T32 HL069765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31 AI145189"],"award-info":[{"award-number":["F31 AI145189"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI151810"],"award-info":[{"award-number":["U01 AI151810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24 GM129541"],"award-info":[{"award-number":["U24 GM129541"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-15-1-0013"],"award-info":[{"award-number":["HDTRA1-15-1-0013"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-13-1-0034"],"award-info":[{"award-number":["HDTRA1-13-1-0034"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stanford-SLAC Cryo-EM Center","award":["S2C2"],"award-info":[{"award-number":["S2C2"]}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,4]]},"abstract":"<jats:p>Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-\u00c5 cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development.<\/jats:p>","DOI":"10.1084\/jem.20212532","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T13:30:01Z","timestamp":1647523801000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-3400","authenticated-orcid":true,"given":"Natasha M.","family":"Kafai","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2725-5826","authenticated-orcid":true,"given":"Lauren E.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 5"},{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-104X","authenticated-orcid":true,"given":"Elad","family":"Binshtein","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-9630","authenticated-orcid":true,"given":"Soila","family":"Sukupolvi-Petty","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-8966","authenticated-orcid":true,"given":"Christina L.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 8"},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA 9"},{"name":"United States Army Research Institute for Infectious Diseases, Fort Detrick, MD 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5911-3112","authenticated-orcid":true,"given":"Jaclyn","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4518-1274","authenticated-orcid":true,"given":"Samantha","family":"Mackin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4101-6642","authenticated-orcid":true,"given":"Arthur S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-292X","authenticated-orcid":true,"given":"Nurgun","family":"Kose","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5230-1532","authenticated-orcid":true,"given":"Robert H.","family":"Carnahan","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 5"},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-095X","authenticated-orcid":true,"given":"Ana","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-1490","authenticated-orcid":true,"given":"Lindsay","family":"Droit","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-9023","authenticated-orcid":true,"given":"Douglas S.","family":"Reed","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 8"},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-6570","authenticated-orcid":true,"given":"Scott A.","family":"Handley","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-7842","authenticated-orcid":true,"given":"William B.","family":"Klimstra","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 8"},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0049-1079","authenticated-orcid":true,"suffix":"Jr.","given":"James E.","family":"Crowe","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 5"},{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 6"},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-6781","authenticated-orcid":true,"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 1"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 2"},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 3"},{"name":"The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"2023072821440204500_bib1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: A comprehensive python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2023072821440204500_bib2","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/BF01309462","article-title":"Localization of four antigenic sites involved in Venezuelan equine encephalomyelitis virus protection","volume":"139","author":"Agapov","year":"1994","journal-title":"Arch. Virol."},{"key":"2023072821440204500_bib3","doi-asserted-by":"publisher","first-page":"721","DOI":"10.2217\/FVL.11.5","article-title":"Endemic Venezuelan equine encephalitis in the Americas: Hidden under the dengue umbrella","volume":"6","author":"Aguilar","year":"2011","journal-title":"Future Virol."},{"key":"2023072821440204500_bib4","doi-asserted-by":"publisher","first-page":"880","DOI":"10.3201\/eid1005.030634","article-title":"Endemic Venezuelan equine encephalitis in northern Peru","volume":"10","author":"Aguilar","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"2023072821440204500_bib5","doi-asserted-by":"publisher","first-page":"4994","DOI":"10.1073\/pnas.0509961103","article-title":"Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation","volume":"103","author":"Anishchenko","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072821440204500_bib6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/jvi.78.1.1-8.2004","article-title":"Generation and characterization of closely related epizootic and enzootic infectious cDNA clones for studying interferon sensitivity and emergence mechanisms of venezuelan equine encephalitis virus","volume":"78","author":"Anishchenko","year":"2004","journal-title":"J. Virol."},{"key":"2023072821440204500_bib7","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41586-021-03963-9","article-title":"Structure of Venezuelan equine encephalitis virus in complex with its LDLRAD3 receptor","volume":"598","author":"Basore","year":"2021","journal-title":"Nature"},{"key":"2023072821440204500_bib8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1093\/oxfordjournals.aje.a120178","article-title":"Attenuation of Venezuelan equine encephalomyelitis virus by in vitro cultivation in guinea pig heart cells","volume":"73","author":"Berge","year":"1961","journal-title":"Am. J. Epidemiol."},{"key":"2023072821440204500_bib9","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1006\/viro.2000.0546","article-title":"Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice","volume":"276","author":"Bernard","year":"2000","journal-title":"Virology"},{"key":"2023072821440204500_bib10","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.actatropica.2016.12.024","article-title":"Culex (Melanoconion) panocossa from peninsular Florida, USA","volume":"167","author":"Blosser","year":"2017","journal-title":"Acta Trop."},{"key":"2023072821440204500_bib11","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1107\/S0907444909007835","article-title":"ALINE: A WYSIWYG protein-sequence alignment editor for publication-quality alignments","volume":"65","author":"Bond","year":"2009","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2023072821440204500_bib12","doi-asserted-by":"publisher","first-page":"11344","DOI":"10.1073\/pnas.0402905101","article-title":"Venezuelan equine encephalitis emergence: Enhanced vector infection from a single amino acid substitution in the envelope glycoprotein","volume":"101","author":"Brault","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072821440204500_bib13","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1097\/00000441-200206000-00004","article-title":"Viral agents as biological weapons and agents of bioterrorism","volume":"323","author":"Bronze","year":"2002","journal-title":"Am. J. Med. Sci."},{"key":"2023072821440204500_bib14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008157","article-title":"Therapeutic monoclonal antibody treatment protects nonhuman primates from severe Venezuelan equine encephalitis virus disease after aerosol exposure","volume":"15","author":"Burke","year":"2019","journal-title":"PLoS Pathog."},{"key":"2023072821440204500_bib15","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1128\/jvi.74.2.644-651.2000","article-title":"Large-plaque mutants of Sindbis virus show reduced binding to heparan sulfate, heightened viremia, and slower clearance from the circulation","volume":"74","author":"Byrnes","year":"2000","journal-title":"J. Virol."},{"key":"2023072821440204500_bib16","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1097\/00007611-198011000-00044","article-title":"Everglades virus infection in man, 1975","volume":"73","author":"Calisher","year":"1980","journal-title":"South Med. J."},{"key":"2023072821440204500_bib17","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1128\/am.25.5.755-762.1973","article-title":"Resistance to arbovirus challenge in mice immediately after vaccination","volume":"25","author":"Casals","year":"1973","journal-title":"Appl. Microbiol."},{"key":"2023072821440204500_bib18","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41591-021-01294-w","article-title":"Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies","volume":"27","author":"Chen","year":"2021","journal-title":"Nat. Med."},{"issue":"17","key":"2023072821440204500_bib100","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"2023072821440204500_bib19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: All-atom structure validation for macromolecular crystallography","volume":"66","author":"Chen","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"issue":"2","key":"2023072821440204500_bib102","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"2023072821440204500_bib20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/imm.12323","article-title":"A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes","volume":"143","author":"Davidson","year":"2014","journal-title":"Immunology"},{"key":"2023072821440204500_bib21","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1084\/jem.20190736","article-title":"Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity","volume":"216","author":"Earnest","year":"2019","journal-title":"J. Exp. Med."},{"key":"2023072821440204500_bib22","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1093\/infdis\/140.5.708","article-title":"Evaluation in humans of a new, inactivated vaccine for Venezuelan equine encephalitis virus (C-84)","volume":"140","author":"Edelman","year":"1979","journal-title":"J. Infect. Dis."},{"key":"2023072821440204500_bib23","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2023072821440204500_bib24","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1107\/S2059798316019276","article-title":"A pipeline approach to single-particle processing in RELION","volume":"73","author":"Fernandez-Leiro","year":"2017","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"2023072821440204500_bib25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1126\/science.aaa8651","article-title":"DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers","volume":"349","author":"Fibriansah","year":"2015","journal-title":"Science"},{"key":"2023072821440204500_bib26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005693","article-title":"Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas","volume":"11","author":"Forrester","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2023072821440204500_bib27","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.cell.2015.10.050","article-title":"Broadly neutralizing alphavirus antibodies bind an epitope on E2 and inhibit entry and egress","volume":"163","author":"Fox","year":"2015","journal-title":"Cell"},{"key":"2023072821440204500_bib28","doi-asserted-by":"publisher","first-page":"16026","DOI":"10.1073\/pnas.1110617108","article-title":"Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence","volume":"108","author":"Gardner","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072821440204500_bib29","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00226-17","article-title":"Antibody preparations from human transchromosomic cows exhibit prophylactic and therapeutic efficacy against Venezuelan equine encephalitis virus","volume":"91","author":"Gardner","year":"2017","journal-title":"J. Virol."},{"key":"2023072821440204500_bib30","doi-asserted-by":"publisher","first-page":"4555","DOI":"10.1128\/JVI.71.6.4555-4563.1997","article-title":"Virus-like particle-induced fusion from without in tissue culture cells: Role of outer-layer proteins VP4 and VP7","volume":"71","author":"Gilbert","year":"1997","journal-title":"J. Virol."},{"key":"2023072821440204500_bib31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.antiviral.2011.01.010","article-title":"A humanised murine monoclonal antibody with broad serogroup specificity protects mice from challenge with Venezuelan equine encephalitis virus","volume":"90","author":"Goodchild","year":"2011","journal-title":"Antivir. Res."},{"key":"2023072821440204500_bib32","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12941-020-00360-4","article-title":"Venezuelan equine encephalitis virus: The problem is not over for tropical America","volume":"19","author":"Guzm\u00e1n-Ter\u00e1n","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"2023072821440204500_bib33","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev.micro.55.1.235","article-title":"Biological weapons\u2013a primer for microbiologists","volume":"55","author":"Hawley","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"issue":"14","key":"2023072821440204500_bib101","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Heng","year":"2009","journal-title":"Bioinformatics"},{"key":"2023072821440204500_bib34","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1016\/j.vaccine.2007.01.034","article-title":"Humanization and mammalian expression of a murine monoclonal antibody against Venezuelan equine encephalitis virus","volume":"25","author":"Hu","year":"2007","journal-title":"Vaccine"},{"key":"2023072821440204500_bib35","doi-asserted-by":"publisher","first-page":"717","DOI":"10.4161\/mabs.28170","article-title":"Human-like antibodies neutralizing Western equine encephalitis virus","volume":"6","author":"H\u00fclseweh","year":"2014","journal-title":"mAbs"},{"key":"2023072821440204500_bib36","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.virol.2011.03.016","article-title":"Treatment of mice with human monoclonal antibody 24h after lethal aerosol challenge with virulent Venezuelan equine encephalitis virus prevents disease but not infection","volume":"414","author":"Hunt","year":"2011","journal-title":"Virology"},{"key":"2023072821440204500_bib37","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1099\/vir.0.81925-0","article-title":"A humanized murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus","volume":"87","author":"Hunt","year":"2006","journal-title":"J. Gen. Virol."},{"key":"2023072821440204500_bib38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000739","article-title":"The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity","volume":"4","author":"Hunt","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2023072821440204500_bib39","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/0042-6822(85)90342-3","article-title":"Biochemical and biological characteristics of epitopes on the E1 glycoprotein of western equine encephalitis virus","volume":"142","author":"Hunt","year":"1985","journal-title":"Virology"},{"key":"2023072821440204500_bib40","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1128\/jcm.19.3.429-431.1984","article-title":"Protective efficacies of live attenuated and formaldehyde-inactivated Venezuelan equine encephalitis virus vaccines against aerosol challenge in hamsters","volume":"19","author":"Jahrling","year":"1984","journal-title":"J. Clin. Microbiol."},{"key":"2023072821440204500_bib41","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1016\/j.celrep.2015.11.043","article-title":"Neutralizing monoclonal antibodies block chikungunya virus entry and release by targeting an epitope critical to viral pathogenesis","volume":"13","author":"Jin","year":"2015","journal-title":"Cell Rep."},{"issue":"Pt 9","key":"2023072821440204500_bib42","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1099\/0022-1317-67-9-1951","article-title":"Molecular determinants of alphavirus neurovirulence: Nucleotide and deduced protein sequence changes during attenuation of Venezuelan equine encephalitis virus","volume":"67","author":"Johnson","year":"1986","journal-title":"J. Gen. Virol."},{"key":"2023072821440204500_bib43","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41564-018-0286-4","article-title":"Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein","volume":"4","author":"Kim","year":"2019","journal-title":"Nat. Microbiol."},{"key":"2023072821440204500_bib44","doi-asserted-by":"publisher","first-page":"4414","DOI":"10.1016\/j.cell.2021.07.006","article-title":"Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope","volume":"184","author":"Kim","year":"2021","journal-title":"Cell"},{"key":"2023072821440204500_bib45","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1128\/JVI.67.3.1269-1277.1993","article-title":"Attenuation of Venezuelan equine encephalitis virus strain TC-83 is encoded by the 5\u2032-noncoding region and the E2 envelope glycoprotein","volume":"67","author":"Kinney","year":"1993","journal-title":"J. Virol."},{"key":"2023072821440204500_bib46","doi-asserted-by":"publisher","first-page":"4697","DOI":"10.1128\/JVI.62.12.4697-4702.1988","article-title":"Recombinant vaccinia virus\/Venezuelan equine encephalitis (VEE) virus protects mice from peripheral VEE virus challenge","volume":"62","author":"Kinney","year":"1988","journal-title":"J. Virol."},{"key":"2023072821440204500_bib47","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0042-6822(89)90347-4","article-title":"The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83","volume":"170","author":"Kinney","year":"1989","journal-title":"Virology"},{"key":"2023072821440204500_bib48","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav3113","article-title":"A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates","volume":"11","author":"Ko","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2023072821440204500_bib49","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18010227","article-title":"An environmental niche model to estimate the potential presence of Venezuelan equine encephalitis virus in Costa Rica","volume":"18","author":"Le\u00f3n","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"2023072821440204500_bib50","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/s0092-8674(01)00303-8","article-title":"The fusion glycoprotein shell of semliki forest virus: An icosahedral assembly primed for fusogenic activation at endosomal pH","volume":"105","author":"Lescar","year":"2001","journal-title":"Cell"},{"key":"2023072821440204500_bib51","doi-asserted-by":"publisher","first-page":"249640","DOI":"10.1155\/2011\/249640","article-title":"Replication of alphaviruses: A review on the entry process of alphaviruses into cells","volume":"2011","author":"Leung","year":"2011","journal-title":"Adv. Virol."},{"key":"2023072821440204500_bib53","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1083\/jcb.200507075","article-title":"Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion","volume":"171","author":"Liao","year":"2005","journal-title":"J. Cell Biol."},{"key":"2023072821440204500_bib106","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/s41586-021-03909-1","article-title":"Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3","volume":"598","author":"Ma","year":"2021","journal-title":"Nature"},{"key":"2023072821440204500_bib54","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41586-020-2915-3","article-title":"LDLRAD3 is a receptor for Venezuelan equine encephalitis virus","volume":"588","author":"Ma","year":"2020","journal-title":"Nature"},{"key":"2023072821440204500_bib55","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jsb.2005.07.007","article-title":"Automated electron microscope tomography using robust prediction of specimen movements","volume":"152","author":"Mastronarde","year":"2005","journal-title":"J. Struct. Biol."},{"key":"2023072821440204500_bib56","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.4049\/jimmunol.129.6.2763","article-title":"Determination of the protective epitopes on the glycoproteins of Venezuelan equine encephalomyelitis virus by passive transfer of monoclonal antibodies","volume":"129","author":"Mathews","year":"1982","journal-title":"J. Immunol."},{"key":"2023072821440204500_bib57","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1084\/jem.76.4.357","article-title":"Induced resistance of the central nervous system to experimental infection with equine encephalomyelitis virus: Neutralization antibody in the central nervous system in relation to cerebral resistance","volume":"76","author":"Morgan","year":"1942","journal-title":"J. Exp. Med."},{"key":"2023072821440204500_bib58","doi-asserted-by":"publisher","first-page":"7210","DOI":"10.1128\/JVI.03690-13","article-title":"Mechanism and significance of cell type-dependent neutralization of flaviviruses","volume":"88","author":"Mukherjee","year":"2014","journal-title":"J. Virol."},{"key":"2023072821440204500_bib59","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/1743-422X-6-206","article-title":"Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains","volume":"6","author":"O\u2019Brien","year":"2009","journal-title":"Virol. J."},{"key":"2023072821440204500_bib60","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1251\/bpo70","article-title":"Negative staining and image classification - powerful tools in modern electron microscopy","volume":"6","author":"Ohi","year":"2004","journal-title":"Biol. Proced. Online"},{"issue":"5","key":"2023072821440204500_bib105","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/nm1240","article-title":"Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus","volume":"11","author":"Oliphant","year":"2005","journal-title":"Nat. Med"},{"key":"2023072821440204500_bib61","doi-asserted-by":"publisher","first-page":"9278","DOI":"10.1128\/jvi.77.17.9278-9286.2003","article-title":"Recombinant Sindbis\/Venezuelan equine encephalitis virus Is highly attenuated and immunogenic","volume":"77","author":"Paessler","year":"2003","journal-title":"J. Virol."},{"issue":"4","key":"2023072821440204500_bib104","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003312","article-title":"Development of a highly protective combination monoclonal antibody therapy against chikungunya virus","volume":"9","author":"Pal","year":"2013","journal-title":"PLoS Pathog"},{"key":"2023072821440204500_bib62","doi-asserted-by":"publisher","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. Comput. Chem."},{"key":"2023072821440204500_bib63","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.virusres.2006.02.003","article-title":"Venezuelan equine encephalitis virus complex-specific monoclonal antibody provides broad protection, in murine models, against airborne challenge with viruses from serogroups I, II and III","volume":"120","author":"Phillpotts","year":"2006","journal-title":"Virus Res."},{"key":"2023072821440204500_bib64","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1016\/s0264-410x(01)00505-9","article-title":"Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus","volume":"20","author":"Phillpotts","year":"2002","journal-title":"Vaccine"},{"key":"2023072821440204500_bib65","doi-asserted-by":"publisher","first-page":"9616","DOI":"10.1128\/JVI.01286-14","article-title":"Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies","volume":"88","author":"Porta","year":"2014","journal-title":"J. Virol."},{"key":"2023072821440204500_bib66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008517","article-title":"Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease","volume":"16","author":"Powell","year":"2020","journal-title":"PLoS Pathog."},{"key":"2023072821440204500_bib67","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","article-title":"cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination","volume":"14","author":"Punjani","year":"2017","journal-title":"Nat. Methods"},{"key":"2023072821440204500_bib68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008061","article-title":"Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins","volume":"15","author":"Quiroz","year":"2019","journal-title":"PLoS Pathog."},{"key":"2023072821440204500_bib69","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1039\/9781849737913-00445","article-title":"Chapter 13 aerosol exposure to pathogenic bacteria and virus particles: Standard operating procedure","volume-title":"Aerobiology: The toxicology of airborne pathogens and toxins","author":"Reed","year":"2016"},{"key":"2023072821440204500_bib70","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/0042-6822(82)90346-4","article-title":"Antigenic analysis of the surface glycoproteins of a Venezuelan equine encephalomyelitis virus (TC-83) using monoclonal antibodies","volume":"118","author":"Roehrig","year":"1982","journal-title":"Virology"},{"key":"2023072821440204500_bib71","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/0042-6822(88)90659-9","article-title":"In vitro mechanisms of monoclonal antibody neutralization of alphaviruses","volume":"165","author":"Roehrig","year":"1988","journal-title":"Virology"},{"key":"2023072821440204500_bib72","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0042-6822(85)90343-5","article-title":"The neutralization site on the E2 glycoprotein of Venezuelan equine encephalomyelitis (TC-83) virus is composed of multiple conformationally stable epitopes","volume":"142","author":"Roehrig","year":"1985","journal-title":"Virology"},{"key":"2023072821440204500_bib73","doi-asserted-by":"publisher","first-page":"959","DOI":"10.3389\/fmicb.2016.00959","article-title":"Neurological sequelae resulting from encephalitic alphavirus infection","volume":"7","author":"Ronca","year":"2016","journal-title":"Front. Microbiol."},{"key":"2023072821440204500_bib74","doi-asserted-by":"publisher","first-page":"380","DOI":"10.30802\/AALAS-CM-18-000027","article-title":"Comparison of aerosol- and percutaneous-acquired Venezuelan equine encephalitis in humans and nonhuman primates for suitability in predicting clinical efficacy under the animal rule","volume":"68","author":"Rusnak","year":"2018","journal-title":"Comp. Med."},{"issue":"14","key":"2023072821440204500_bib103","doi-asserted-by":"publisher","first-page":"7005","DOI":"10.1128\/JVI.00586-11","article-title":"Neutralizing monoclonal antibodies against hepatitis C virus E2 protein bind discontinuous epitopes and inhibit infection at a postattachment step","volume":"85","author":"Sabo","year":"2011","journal-title":"J. Virol"},{"key":"2023072821440204500_bib75","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","article-title":"RELION: Implementation of a bayesian approach to cryo-EM structure determination","volume":"180","author":"Scheres","year":"2012","journal-title":"J. Struct. Biol."},{"key":"2023072821440204500_bib76","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3390\/v11020164","article-title":"Current understanding of the molecular basis of Venezuelan equine encephalitis virus pathogenesis and vaccine development","volume":"11","author":"Sharma","year":"2019","journal-title":"Viruses"},{"key":"2023072821440204500_bib77","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/s0166-3542(02)00203-6","article-title":"Viruses of the Bunya- and Togaviridae families: Potential as bioterrorism agents and means of control","volume":"57","author":"Sidwell","year":"2003","journal-title":"Antivir. Res."},{"key":"2023072821440204500_bib78","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1128\/JVI.03116-13","article-title":"A single-amino-acid polymorphism in chikungunya virus e2 glycoprotein influences glycosaminoglycan utilization","volume":"88","author":"Silva","year":"2014","journal-title":"J. Virol."},{"key":"2023072821440204500_bib79","doi-asserted-by":"publisher","first-page":"0027-2014","DOI":"10.1128\/microbiolspec.AID-0027-2014","article-title":"Use of human hybridoma technology to isolate human monoclonal antibodies","volume":"3","author":"Smith","year":"2015","journal-title":"Microbiol. Spectr."},{"key":"2023072821440204500_bib80","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.chom.2015.06.009","article-title":"Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus","volume":"18","author":"Smith","year":"2015","journal-title":"Cell Host Microbe"},{"key":"2023072821440204500_bib81","doi-asserted-by":"publisher","first-page":"10648","DOI":"10.1073\/pnas.92.23.10648","article-title":"Putative receptor binding sites on alphaviruses as visualized by cryoelectron microscopy","volume":"92","author":"Smith","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072821440204500_bib82","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The alphaviruses: Gene expression, replication, and evolution","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. Rev."},{"key":"2023072821440204500_bib83","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1128\/jvi.02990-13","article-title":"Stable, high-level expression of reporter proteins from improved alphavirus expression vectors to track replication and dissemination during encephalitic and arthritogenic disease","volume":"88","author":"Sun","year":"2014","journal-title":"J. Virology"},{"key":"2023072821440204500_bib84","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000453","article-title":"A therapeutic antibody against west nile virus neutralizes infection by blocking fusion within endosomes","volume":"5","author":"Thompson","year":"2009","journal-title":"PLoS Pathog."},{"key":"2023072821440204500_bib85","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210174","article-title":"Broadly neutralizing monoclonal antibodies protect against multiple tick-borne flaviviruses","volume":"218","author":"Vanblargan","year":"2021","journal-title":"J. Exp. Med."},{"key":"2023072821440204500_bib86","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nature09555","article-title":"Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography","volume":"468","author":"Voss","year":"2010","journal-title":"Nature"},{"key":"2023072821440204500_bib87","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.cell.2017.09.002","article-title":"A human Bi-specific antibody against zika virus with high therapeutic potential","volume":"171","author":"Wang","year":"2017","journal-title":"Cell"},{"key":"2023072821440204500_bib88","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.antiviral.2012.04.002","article-title":"Alphaviruses: Population genetics and determinants of emergence","volume":"94","author":"Weaver","year":"2012","journal-title":"Antivir. Res."},{"key":"2023072821440204500_bib89","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1128\/JVI.02792-15","article-title":"Dissecting the role of E2 protein domains in alphavirus pathogenicity","volume":"90","author":"Weger-Lucarelli","year":"2015","journal-title":"J. Virol."},{"key":"2023072821440204500_bib90","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1016\/j.cell.2020.11.011","article-title":"Human antibodies protect against aerosolized eastern equine encephalitis virus infection","volume":"183","author":"Williamson","year":"2020","journal-title":"Cell"},{"key":"2023072821440204500_bib91","doi-asserted-by":"publisher","first-page":"4430","DOI":"10.1016\/j.cell.2021.07.033","article-title":"Therapeutic alphavirus cross-reactive E1 human antibodies inhibit viral egress","volume":"184","author":"Williamson","year":"2021","journal-title":"Cell"},{"key":"2023072821440204500_bib92","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1093\/oxfordjournals.aje.a120942","article-title":"Antigenic variants of Venezuelan equine encephalitis virus: Their geographic distribution and epidemiologic significance","volume":"89","author":"Young","year":"1969","journal-title":"Am. J. Epidemiol."},{"key":"2023072821440204500_bib93","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.jim.2008.04.008","article-title":"An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies","volume":"336","author":"Yu","year":"2008","journal-title":"J. Immunol. Methods"},{"key":"2023072821440204500_bib94","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.vetmic.2009.08.023","article-title":"Encephalitic alphaviruses","volume":"140","author":"Zacks","year":"2010","journal-title":"Vet. Microbiol."},{"key":"2023072821440204500_bib95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jsb.2015.11.003","article-title":"Gctf: Real-time CTF determination and correction","volume":"193","author":"Zhang","year":"2016","journal-title":"J. Struct. Biol."},{"key":"2023072821440204500_bib96","doi-asserted-by":"publisher","first-page":"3854","DOI":"10.1038\/emboj.2011.261","article-title":"4.4 \u00c5 cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus","volume":"30","author":"Zhang","year":"2011","journal-title":"EMBO J."},{"key":"2023072821440204500_bib97","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/s41586-018-0121-3","article-title":"Mxra8 is a receptor for multiple arthritogenic alphaviruses","volume":"557","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"2023072821440204500_bib98","doi-asserted-by":"publisher","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"2023072821440204500_bib99","doi-asserted-by":"publisher","first-page":"27637","DOI":"10.1073\/pnas.2008051117","article-title":"Structural basis of Chikungunya virus inhibition by monoclonal antibodies","volume":"117","author":"Zhou","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20212532\/1833538\/jem_20212532.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20212532\/1833538\/jem_20212532.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T21:45:13Z","timestamp":1690580713000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/219\/4\/e20212532\/213072\/Neutralizing-antibodies-protect-mice-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":105,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4,4]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20212532","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]},"article-number":"e20212532"}}