{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:37:48Z","timestamp":1792791468456,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2019.00200","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T11:32:56Z","timestamp":1559820776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Molecular Simulations Reveal the Role of Antibody Fine Specificity and Viral Maturation State on Antibody-Dependent Enhancement of Infection in Dengue Virus"],"prefix":"10.3389","volume":"9","author":[{"given":"Daniel R.","family":"Ripoll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Wallqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidhartha","family":"Chaudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/S1473-3099(16)30168-2","article-title":"The risks behind Dengvaxia recommendation","volume":"16","author":"Aguiar","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/nature18938","article-title":"Structural basis of potent Zika-dengue virus antibody cross-neutralization","volume":"536","author":"Barba-Spaeth","year":"2016","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.chom.2010.08.007","article-title":"The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity","volume":"8","author":"Beltramello","year":"2010","journal-title":"Cell Host Microbe"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5804","DOI":"10.1073\/pnas.88.13.5804","article-title":"Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides","volume":"88","author":"Beroza","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B5","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1002\/9783527622023","volume-title":"Enzyme Kinetics. Principles and Methods.","author":"Bisswanger","year":"2008"},{"key":"B7","doi-asserted-by":"publisher","first-page":"7439","DOI":"10.1073\/pnas.1200566109","article-title":"Identification of human neutralizing antibodies that bind to complex epitopes on dengue virions","volume":"109","author":"De Alwis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1126\/science.1185181","article-title":"Cross-reacting antibodies enhance dengue virus infection in humans","volume":"328","author":"Dejnirattisai","year":"2010","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/ni.3058","article-title":"A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus","volume":"16","author":"Dejnirattisai","year":"2015","journal-title":"Nat. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.virol.2010.12.020","article-title":"Antibody-mediated neutralization of flaviviruses: a reductionist view","volume":"411","author":"Dowd","year":"2011","journal-title":"Virology"},{"key":"B12","volume-title":"Biophysical Chemistry.","author":"Edsall","year":"1958"},{"key":"B13","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1126\/science.aaa8651","article-title":"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":"B14","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1016\/j.vaccine.2018.03.055","article-title":"Delineating the serotype-specific neutralizing antibody response to a live attenuated tetravalent dengue vaccine","volume":"36","author":"Gromowski","year":"2018","journal-title":"Vaccine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/S0140-6736(14)60572-9","article-title":"Dengue","volume":"385","author":"Guzman","year":"2015","journal-title":"Lancet"},{"key":"B16","first-page":"350","article-title":"Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion","volume":"42","author":"Halstead","year":"1970","journal-title":"Yale J. Biol. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1016\/S0140-6736(07)61687-0","article-title":"Dengue","volume":"370","author":"Halstead","year":"2007","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1084\/jem.146.1.201","article-title":"Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody","volume":"146","author":"Halstead","year":"1977","journal-title":"J. Exp. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"830","DOI":"10.4269\/ajtmh.1982.31.830","article-title":"Dengue virus-specific and flavivirus group determinants identified with monoclonal antibodies by indirect immunofluorescence","volume":"31","author":"Henchal","year":"1982","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8353","DOI":"10.1128\/JVI.00696-10","article-title":"Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles","volume":"84","author":"Junjhon","year":"2010","journal-title":"J. Virol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"10776","DOI":"10.1128\/JVI.01180-08","article-title":"Differential modulation of prM cleavage, extracellular particle distribution, and virus infectivity by conserved residues at nonfurin consensus positions of the dengue virus pr-M junction","volume":"82","author":"Junjhon","year":"2008","journal-title":"J. Virol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3179","DOI":"10.1016\/S0264-410X(01)00020-2","article-title":"Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers","volume":"19","author":"Kanesa-Thasan","year":"2001","journal-title":"Vaccine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"18950","DOI":"10.1073\/pnas.1011036107","article-title":"Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354","volume":"107","author":"Kaufmann","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"7700","DOI":"10.1128\/JVI.00197-13","article-title":"Immature and mature dengue serotype 1 virus structures provide insight into the maturation process","volume":"87","author":"Kostyuchenko","year":"2013","journal-title":"J. Virol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e2357","DOI":"10.1371\/journal.pntd.0002357","article-title":"Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year","volume":"7","author":"Montoya","year":"2013","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e1000060","DOI":"10.1371\/journal.ppat.1000060","article-title":"Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization","volume":"4","author":"Nelson","year":"2008","journal-title":"PLoS Pathog."},{"key":"B28","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nature03956","article-title":"Structural basis of West Nile virus neutralization by a therapeutic antibody","volume":"437","author":"Nybakken","year":"2005","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0065-2776(01)77018-6","article-title":"The antiviral activity of antibodies in vitro and in vivo","volume":"77","author":"Parren","year":"2001","journal-title":"Adv. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.mib.2008.06.004","article-title":"Structural proteomics of dengue virus","volume":"11","author":"Perera","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.chom.2007.03.002","article-title":"The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection","volume":"1","author":"Pierson","year":"2007","journal-title":"Cell Host Microbe"},{"key":"B32","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/embor.2011.75","article-title":"Maturation of flaviviruses starts from one or more icosahedrally independent nucleation centres","volume":"12","author":"Plevka","year":"2011","journal-title":"EMBO Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0006191","DOI":"10.1371\/journal.pntd.0006191","article-title":"A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice","volume":"12","author":"Ramasamy","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1016\/j.bpj.2016.09.003","article-title":"Modeling the role of epitope arrangement on antibody binding stoichiometry in flaviviruses","volume":"111","author":"Ripoll","year":"2016","journal-title":"Biophys. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"15411","DOI":"10.1038\/ncomms15411","article-title":"Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope","volume":"8","author":"Rouvinski","year":"2017","journal-title":"Nat. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nature14130","article-title":"Recognition determinants of broadly neutralizing human antibodies against dengue viruses","volume":"520","author":"Rouvinski","year":"2015","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.4269\/ajtmh.1952.1.30","article-title":"Research on dengue during World War II","volume":"1","author":"Sabin","year":"1952","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41586-018-0157-4","article-title":"Reconstruction of antibody dynamics and infection histories to evaluate dengue risk","volume":"557","author":"Salje","year":"2018","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/oxfordjournals.aje.a113932","article-title":"Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak","volume":"120","author":"Sangkawibha","year":"1984","journal-title":"Am. J. Epidemiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"235","DOI":"10.4269\/ajtmh.13-0742","article-title":"Sequential episodes of dengue\u2014Puerto Rico, 2005\u20132010","volume":"91","author":"Sharp","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B41","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1128\/JVI.01805-15","article-title":"Dengue virus prM-specific human monoclonal antibodies with virus replication-enhancing properties recognize a single immunodominant antigenic site","volume":"90","author":"Smith","year":"2016","journal-title":"J. Virol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1128\/JVI.06335-11","article-title":"Persistence of circulating memory B cell clones with potential for dengue virus disease enhancement for decades following infection","volume":"86","author":"Smith","year":"2012","journal-title":"J. Virol."},{"key":"B43","volume-title":"Multiple Equilibria in Proteins.","author":"Steinhardt","year":"1969"},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","first-page":"5333","DOI":"10.1021\/ja01577a001","article-title":"Theory of protein titration curves. I. General equations for impenetrable spheres","volume":"79","author":"Tanford","year":"1957","journal-title":"J. Am. Chem. Soc."},{"key":"B46","doi-asserted-by":"publisher","first-page":"L81","DOI":"10.1086\/310310","article-title":"An icosahedron-based method for pixelizing a cellestial sphere","volume":"470","author":"Tegmark","year":"1996","journal-title":"Astrophys. J. Lett."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e1000244","DOI":"10.1371\/journal.ppat.1000244","article-title":"Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells","volume":"4","author":"Van Der Schaar","year":"2008","journal-title":"PLoS Pathog."},{"key":"B48","doi-asserted-by":"publisher","first-page":"8909","DOI":"10.1128\/JVI.00472-13","article-title":"Obstruction of dengue virus maturation by fab fragments of the 2H2 antibody","volume":"87","author":"Wang","year":"2013","journal-title":"J. Virol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.1128\/JVI.00216-15","article-title":"Dengue virus infection with highly neutralizing levels of cross-reactive antibodies causes acute lethal small intestinal pathology without a high level of viremia in mice","volume":"89","author":"Watanabe","year":"2015","journal-title":"J. Virol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"420867","DOI":"10.1155\/2015\/420867","article-title":"Dengue patients exhibit higher levels of prM and E antibodies than their asymptomatic counterparts","volume":"2015","author":"Yeo","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1126\/science.1153264","article-title":"Structure of the immature dengue virus at low pH primes proteolytic maturation","volume":"319","author":"Yu","year":"2008","journal-title":"Science"},{"key":"B52","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nsb990","article-title":"Visualization of membrane protein domains by cryo-electron microscopy of dengue virus","volume":"10","author":"Zhang","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nsmb.2463","article-title":"Cryo-EM structure of the mature dengue virus at 3.5-A resolution","volume":"20","author":"Zhang","year":"2013","journal-title":"Nat. Struct. Mol. Biol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00200\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T11:32:59Z","timestamp":1559820779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00200\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,6]]},"references-count":53,"alternative-id":["10.3389\/fcimb.2019.00200"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2019.00200","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,6]]},"article-number":"200"}}