{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:10:41Z","timestamp":1783577441891,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Flavivirus E protein induces protective immunity, and its Abs cause serious problems for serodiagnosis because of the difficulty in differentiating cross-reactive Abs. Moreover, cross-reactive Abs may increase disease severity after secondary Flavivirus infections via Ab-dependent enhancement. Cross-reactive epitopes are therefore critical for understanding serodiagnosis and improving the general knowledge of Flavivirus infections. A minimal epitope, 227GSSAGTWQN235, was identified by a neutralizing mAb 1G2 against duck Tembusu virus (DTMUV), which recognized only monomer E protein under nonreducing conditions. It was unexpectedly found that mutations in the epitope residues G231 or W233 completely abolished reactivity to 1G2 and sera from mice infected with Japanese encephalitis virus, West Nile virus, and Zika virus. An immunofluorescence assay confirmed that mAb 1G2 could cross-react with the E proteins from Japanese encephalitis virus, West Nile virus, and Zika virus. Protein and virus modeling revealed that the epitope was surface accessible in the mature virus and located in the hi loop of domain II. The neutralization of DTMUV by 1G2 played a clear therapeutic role in mouse models. The passive transfer of 1G2 resulted in 100% survival, reduced weight loss, and the complete clearance of DTMUV from the blood of BALB\/c mice. Our findings document, for the first time to our knowledge, that mAb 1G2 targets the cross-reactive epitope on the hi loop of domain II in the E protein and might be of potential therapeutic value in treating DTMUV infection and improve the understanding of the issues related to serodiagnosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1901352","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T20:25:14Z","timestamp":1583353514000},"page":"1836-1848","source":"Crossref","is-referenced-by-count":13,"title":["A Novel Neutralizing Antibody Targeting a Unique Cross-Reactive Epitope on the hi Loop of Domain II of the Envelope Protein Protects Mice against Duck Tembusu Virus"],"prefix":"10.1093","volume":"204","author":[{"given":"Xueming","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-0745","authenticated-orcid":false,"given":"Chenxi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhou","family":"Wulin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-0372","authenticated-orcid":false,"given":"Jyung-Hurng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Bioinformatics, National Chung Hsing University , Taichung City 40227 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2315-7038","authenticated-orcid":false,"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences , Harbin 150069 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"2025030417511244700_r1","first-page":"1101","volume-title":"Fields Virology","author":"Lindenbach","year":"2007","edition":"5th Ed."},{"key":"2025030417511244700_r2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aal4365","article-title":"Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity","volume":"356","author":"Bardina","year":"2017","journal-title":"Science"},{"key":"2025030417511244700_r3","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/ni.3515","article-title":"Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus","volume":"17","author":"Dejnirattisai","year":"2016","journal-title":"Nat. Immunol."},{"key":"2025030417511244700_r4","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"2025030417511244700_r5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0018106","article-title":"Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus","volume":"6","author":"Su","year":"2011","journal-title":"PLoS One"},{"key":"2025030417511244700_r6","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1128\/JCM.00655-12","article-title":"Adapted Tembusu-like virus in chickens and geese in China","volume":"50","author":"Liu","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"2025030417511244700_r7","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.virusres.2013.06.010","article-title":"An adapted duck Tembusu virus induces systemic infection and mediates antibody-dependent disease severity in mice","volume":"176","author":"Liu","year":"2013","journal-title":"Virus Res."},{"key":"2025030417511244700_r8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/tbed.12085","article-title":"Tembusu virus in human, China","volume":"60","author":"Tang","year":"2013","journal-title":"Transbound. Emerg. Dis."},{"key":"2025030417511244700_r9","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s11262-013-0966-3","article-title":"Molecular characterization of a duck Tembusu virus from China","volume":"47","author":"Bai","year":"2013","journal-title":"Virus Genes"},{"key":"2025030417511244700_r10","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00427-18","article-title":"A single mutation at position 156 in the envelope protein of Tembusu virus is responsible for virus tissue tropism and transmissibility in ducks","author":"Yan","year":"2018","journal-title":"J. Virol."},{"key":"2025030417511244700_r11","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1128\/JVI.79.2.1223-1231.2005","article-title":"Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein","volume":"79","author":"Modis","year":"2005","journal-title":"J. Virol."},{"key":"2025030417511244700_r12","doi-asserted-by":"crossref","first-page":"11467","DOI":"10.1128\/JVI.01125-06","article-title":"Crystal structure of the West Nile virus envelope glycoprotein","volume":"80","author":"Nybakken","year":"2006","journal-title":"J. Virol."},{"key":"2025030417511244700_r13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/viro.1998.9200","article-title":"Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica","volume":"246","author":"Roehrig","year":"1998","journal-title":"Virology"},{"key":"2025030417511244700_r14","doi-asserted-by":"crossref","first-page":"7769","DOI":"10.1128\/JVI.75.16.7769-7773.2001","article-title":"Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells","volume":"75","author":"Crill","year":"2001","journal-title":"J. Virol."},{"key":"2025030417511244700_r15","doi-asserted-by":"crossref","first-page":"13975","DOI":"10.1128\/JVI.78.24.13975-13986.2004","article-title":"Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes","volume":"78","author":"Crill","year":"2004","journal-title":"J. Virol."},{"key":"2025030417511244700_r16","doi-asserted-by":"crossref","first-page":"9557","DOI":"10.1128\/JVI.00080-06","article-title":"Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic sites","volume":"80","author":"Stiasny","year":"2006","journal-title":"J. Virol."},{"key":"2025030417511244700_r17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1128\/JVI.02273-12","article-title":"Mechanistic study of broadly neutralizing human monoclonal antibodies against dengue virus that target the fusion loop","volume":"87","author":"Costin","year":"2013","journal-title":"J. Virol."},{"key":"2025030417511244700_r18","doi-asserted-by":"crossref","first-page":"6631","DOI":"10.1128\/JVI.00316-08","article-title":"Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II","volume":"82","author":"Lai","year":"2008","journal-title":"J. Virol."},{"key":"2025030417511244700_r19","doi-asserted-by":"crossref","DOI":"10.1017\/S1462399408000665","article-title":"Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection","volume":"10","author":"Pierson","year":"2008","journal-title":"Expert Rev. Mol. Med."},{"key":"2025030417511244700_r20","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00873-13","article-title":"The potent and broadly neutralizing human dengue virus-specific monoclonal antibody 1C19 reveals a unique cross-reactive epitope on the bc loop of domain II of the envelope protein","author":"Smith","year":"2013","journal-title":"mBio"},{"key":"2025030417511244700_r21","doi-asserted-by":"crossref","DOI":"10.3390\/v8110306","article-title":"Epitope identification and application for diagnosis of duck Tembusu virus infections in ducks","author":"Li","year":"2016","journal-title":"Viruses"},{"key":"2025030417511244700_r22","doi-asserted-by":"crossref","first-page":"36288","DOI":"10.1038\/srep36288","article-title":"Identification of a new broadly cross-reactive epitope within domain III of the duck tembusu virus E protein","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"2025030417511244700_r23","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00705-014-2312-z","article-title":"Characterization of monoclonal antibodies against duck Tembusu virus E protein: an antigen-capture ELISA for the detection of Tembusu virus infection","volume":"160","author":"Bai","year":"2015","journal-title":"Arch. Virol."},{"key":"2025030417511244700_r24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11262-015-1200-2","article-title":"Duck tembusu virus and its envelope protein induce programmed cell death","volume":"51","author":"Shaozhou","year":"2015","journal-title":"Virus Genes"},{"key":"2025030417511244700_r25","doi-asserted-by":"crossref","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":"2025030417511244700_r26","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s00705-009-0426-5","article-title":"Production and characterization of anti-dengue capsid antibodies suggesting the N terminus region covering the first 20 amino acids of dengue virus capsid protein is predominantly immunogenic in mice","volume":"154","author":"Puttikhunt","year":"2009","journal-title":"Arch. Virol."},{"key":"2025030417511244700_r27","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.virusres.2011.12.006","article-title":"Antigenic analysis monoclonal antibodies against different epitopes of \u03c3B protein of Muscovy duck reovirus","volume":"163","author":"Li","year":"2012","journal-title":"Virus Res."},{"key":"2025030417511244700_r28","first-page":"71","article-title":"DNASTAR\u2019s Lasergene sequence analysis software","volume":"132","author":"Burland","year":"2000","journal-title":"Methods Mol. Biol."},{"key":"2025030417511244700_r29","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1128\/JVI.06072-11","article-title":"Crystal structure of the Japanese encephalitis virus envelope protein","volume":"86","author":"Luca","year":"2012","journal-title":"J. Virol."},{"key":"2025030417511244700_r30","volume-title":"The PyMOL Molecular Graphics System","author":"DeLano","year":"2004"},{"key":"2025030417511244700_r31","volume-title":"Curr. Protoc. Protein Sci.","author":"Eswar","year":"2007"},{"key":"2025030417511244700_r32","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1093\/nar\/gkg601","article-title":"POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level","volume":"31","author":"Cavallo","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2025030417511244700_r33","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00705-006-0903-z","article-title":"Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses","volume":"152","author":"Kuno","year":"2007","journal-title":"Arch. Virol."},{"key":"2025030417511244700_r34","doi-asserted-by":"crossref","first-page":"11000","DOI":"10.1128\/JVI.01735-06","article-title":"Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes","volume":"80","author":"Kanai","year":"2006","journal-title":"J. Virol."},{"key":"2025030417511244700_r35","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1093\/nar\/gki633","article-title":"Prediction of solvent accessibility and sites of deleterious mutations from protein sequence","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2025030417511244700_r36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1389450043490668","article-title":"Epitope identification and discovery using phage display libraries: applications in vaccine development and diagnostics","volume":"5","author":"Wang","year":"2004","journal-title":"Curr. Drug Targets"},{"key":"2025030417511244700_r37","doi-asserted-by":"crossref","first-page":"7981","DOI":"10.1021\/bi980148j","article-title":"A mutational analysis of binding interactions in an antigen-antibody protein-protein complex","volume":"37","author":"Dall\u2019Acqua","year":"1998","journal-title":"Biochemistry"},{"key":"2025030417511244700_r38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1006\/jmbi.1993.1611","article-title":"Comparison of a structural and a functional epitope","volume":"234","author":"Cunningham","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2025030417511244700_r39","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature18952","article-title":"Vaccine protection against Zika virus from Brazil","volume":"536","author":"Larocca","year":"2016","journal-title":"Nature"},{"key":"2025030417511244700_r40","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1128\/am.25.4.539-544.1973","article-title":"Yellow fever vaccine: direct challenge of monkeys given graded doses of 17D vaccine","volume":"25","author":"Mason","year":"1973","journal-title":"Appl. Microbiol."},{"key":"2025030417511244700_r41","doi-asserted-by":"crossref","first-page":"7559","DOI":"10.1016\/j.vaccine.2007.08.024","article-title":"Field effectiveness of vaccination against tick-borne encephalitis","volume":"25","author":"Heinz","year":"2007","journal-title":"Vaccine"},{"key":"2025030417511244700_r42","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1016\/j.vaccine.2005.07.002","article-title":"Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004","volume":"23","author":"Hombach","year":"2005","journal-title":"Vaccine"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/204\/7\/1836\/61358774\/ji1901352.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/204\/7\/1836\/61358774\/ji1901352.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T18:07:29Z","timestamp":1741111649000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/204\/7\/1836\/7943743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1901352","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2020,4,1]]}}}