{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:05Z","timestamp":1786978085856,"version":"build-2736575974"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,10]],"date-time":"2014-02-10T00:00:00Z","timestamp":1391990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>\n                    Dengue fever is the most important vector\u2010borne viral disease. Four serotypes of dengue virus, DENV1 to DENV4, coexist. Secondary infection by a different serotype is a risk factor for severe dengue. Monoclonal antibody mAb4E11 neutralizes the four serotypes of DENV with varying efficacies by recognizing an epitope located within domain\u2010III (ED3) of the viral envelope (E) protein. To better understand the cross\u2010reactivities between mAb4E11 and the four serotypes of DENV, we constructed mutations in both Fab4E11 fragment and ED3, and we searched for indirect interactions in the crystal structures of the four complexes. According to the serotype, 7 to 12 interactions are mediated by one water molecule, 1 to 10 by two water molecules, and several of these interactions are conserved between serotypes. Most interfacial water molecules make hydrogen bonds with both antibody and antigen. Some residues or atomic groups are engaged in both direct and water\u2010mediated interactions. The doubly\u2010indirect interactions are more numerous in the complex of lowest affinity. The third complementarity determining region of the light chain (L\u2010CDR3) of mAb4E11 does not contact ED3. The structures and double\u2010mutant thermodynamic cycles showed that the effects of (hyper)\u2010mutations in L\u2010CDR3 on affinity were caused by conformational changes and indirect interactions with ED3 through other CDRs. Exchanges of residues between ED3 serotypes showed that their effects on affinity were context dependent. Thus, conformational changes, structural context, and indirect interactions should be included when studying cross\u2010reactivity between antibodies and different serotypes of viral antigens for a better design of diagnostics, vaccine, and therapeutic tools against DENV and other\n                    <jats:italic>Flaviviruses<\/jats:italic>\n                    . Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/jmr.2352","type":"journal-article","created":{"date-parts":[[2014,2,10]],"date-time":"2014-02-10T21:57:25Z","timestamp":1392069445000},"page":"205-214","source":"Crossref","is-referenced-by-count":15,"title":["Direct and indirect interactions in the recognition between a cross\u2010neutralizing antibody and the four serotypes of dengue virus"],"prefix":"10.1002","volume":"27","author":[{"given":"Olesia","family":"Lisova","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit of Molecular Prevention and Therapy of Human Diseases, Department of Infection and Epidemiology  rue du Dr. Roux F\u201075015 Paris France"},{"name":"CNRS, URA3012  rue du Dr. Roux F\u201075015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Belkadi","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit of Molecular Prevention and Therapy of 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