Please use this identifier to cite or link to this item: https://doi.org/10.1128/JVI.00406-17
Title: Structural Mimicry of the Dengue Virus Envelope Glycoprotein Revealed by the Crystallographic Study of an Idiotype-Anti-idiotype Fab Complex
Authors: Wong, Yee Hwa
Goh, Boon Chong
Lim, She Yah
Teo, En Wei 
Lim, Angeline PC 
Dedon, Pete C
Hanson, Brendon J 
MacAry, Paul A 
Lescar, Julien 
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
dengue virus
idiotypic antibody
idiotype-anti-idiotype Fab complex
antigen mimicry
virus-antibody complex
X-ray crystallography
CRYSTAL-STRUCTURE
IDIOTOPE
Issue Date: 1-Sep-2017
Publisher: AMER SOC MICROBIOLOGY
Citation: Wong, Yee Hwa, Goh, Boon Chong, Lim, She Yah, Teo, En Wei, Lim, Angeline PC, Dedon, Pete C, Hanson, Brendon J, MacAry, Paul A, Lescar, Julien (2017-09-01). Structural Mimicry of the Dengue Virus Envelope Glycoprotein Revealed by the Crystallographic Study of an Idiotype-Anti-idiotype Fab Complex. JOURNAL OF VIROLOGY 91 (17). ScholarBank@NUS Repository. https://doi.org/10.1128/JVI.00406-17
Abstract: A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic flaviviruses such as dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody, termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope, a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins. This comparison reveals that the footprints left by E1 and E on HM14c10 largely overlap, explaining why the formation of binary complexes is mutually exclusive. Structural mimicry of the DENV E epitope by the E1 combining site is achieved via the formation of numerous interactions with heavy chain complementarity domain regions (CDRs) of HM14c10, while fewer interactions are observed with its light chain than for the E protein. We show that E1 can be utilized to detect HM14c10-like antibodies in sera from patients who recovered from DENV-1, infection suggesting that this is a public (common) idiotype. These data demonstrate the utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses and suggest routes for the improvement of E "mimicry" by E1 by increasing its recognition of the Fab HM14c10 light chain CDRs.
Source Title: JOURNAL OF VIROLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/239536
ISSN: 0022-538X
1098-5514
DOI: 10.1128/JVI.00406-17
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