title: DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.
abstract: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Guntur
authors.initials: G
authors.lastname: Fibriansah
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Kristie D
authors.initials: KD
authors.lastname: Ibarra
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Thiam-Seng
authors.initials: TS
authors.lastname: Ng
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN, USA. The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Tan
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Xin-Ni
authors.initials: XN
authors.lastname: Lim
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Justin S G
authors.initials: JS
authors.lastname: Ooi
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Kostyuchenko
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA. Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore. Centre for BioImaging Sciences, National University of Singapore, Singapore. sheemei.lok@duke-nus.edu.sg james.crowe@vanderbilt.edu.
authors.forename: Shee-Mei
authors.initials: SM
authors.lastname: Lok
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000648:ultrastructure*; D057134:Antibodies, Neutralizing / Q000648:ultrastructure*; D060085:Coinfection / Q000276:immunology; D003429:Cross Reactions; D020285:Cryoelectron Microscopy; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D006801:Humans; D051379:Mice; D065288:Serogroup; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D014759:Viral Envelope Proteins