A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface
Abstract Dengue virus (DENV), which consists of four serotypes (DENV1‐4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross‐reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype‐s...
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doaj-5a2bbed09b4a44cd9ed0e1bdfbeffee22021-08-02T10:24:29ZengWileyEMBO Molecular Medicine1757-46761757-46842014-03-016335837110.1002/emmm.201303404A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surfaceGuntur Fibriansah0Joanne L Tan1Scott A Smith2Adamberage R deAlwis3Thiam‐Seng Ng4Victor A Kostyuchenko5Kristie D Ibarra6Jiaqi Wang7Eva Harris8Aravinda deSilva9James E Crowe Jr10Shee‐Mei Lok11Program in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeProgram in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeDepartment of Medicine Vanderbilt University Nashville TN USADepartment of Microbiology and Immunology University of North Carolina School of Medicine Chapel Hill NC USAProgram in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeProgram in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeDivision of Infectious Diseases and Vaccinology School of Public Health University of California Berkeley CA USAProgram in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeDivision of Infectious Diseases and Vaccinology School of Public Health University of California Berkeley CA USADepartment of Microbiology and Immunology University of North Carolina School of Medicine Chapel Hill NC USAThe Vanderbilt Vaccine Center Vanderbilt University Nashville TN USAProgram in Emerging Infectious Diseases Duke–NUS Graduate Medical School Singapore City SingaporeAbstract Dengue virus (DENV), which consists of four serotypes (DENV1‐4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross‐reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype‐specific and bind to quaternary structure‐dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo‐EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI‐DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection.https://doi.org/10.1002/emmm.201303404cryoEMdengue virushuman antibodyneutralizationstructure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guntur Fibriansah Joanne L Tan Scott A Smith Adamberage R deAlwis Thiam‐Seng Ng Victor A Kostyuchenko Kristie D Ibarra Jiaqi Wang Eva Harris Aravinda deSilva James E Crowe Jr Shee‐Mei Lok |
spellingShingle |
Guntur Fibriansah Joanne L Tan Scott A Smith Adamberage R deAlwis Thiam‐Seng Ng Victor A Kostyuchenko Kristie D Ibarra Jiaqi Wang Eva Harris Aravinda deSilva James E Crowe Jr Shee‐Mei Lok A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface EMBO Molecular Medicine cryoEM dengue virus human antibody neutralization structure |
author_facet |
Guntur Fibriansah Joanne L Tan Scott A Smith Adamberage R deAlwis Thiam‐Seng Ng Victor A Kostyuchenko Kristie D Ibarra Jiaqi Wang Eva Harris Aravinda deSilva James E Crowe Jr Shee‐Mei Lok |
author_sort |
Guntur Fibriansah |
title |
A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface |
title_short |
A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface |
title_full |
A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface |
title_fullStr |
A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface |
title_full_unstemmed |
A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface |
title_sort |
potent anti‐dengue human antibody preferentially recognizes the conformation of e protein monomers assembled on the virus surface |
publisher |
Wiley |
series |
EMBO Molecular Medicine |
issn |
1757-4676 1757-4684 |
publishDate |
2014-03-01 |
description |
Abstract Dengue virus (DENV), which consists of four serotypes (DENV1‐4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross‐reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype‐specific and bind to quaternary structure‐dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo‐EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI‐DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection. |
topic |
cryoEM dengue virus human antibody neutralization structure |
url |
https://doi.org/10.1002/emmm.201303404 |
work_keys_str_mv |
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