Details

Autor(en) / Beteiligte

• Li, Jie
• Watterson, Daniel
• Chang, Chiung-Wen
• Che, Xiao-Yan
• Li, Xiao-Quan
• Ericsson, Daniel J.
• Qiu, Li-Wen
• Cai, Jian-Piao
• Chen, Jing
• Fry, Scott R.
• Cheung, Stacey T.M.
• Cooper, Matthew A.
• Young, Paul R.
• Kobe, Bostjan

Titel

Structural and Functional Characterization of a Cross-Reactive Dengue Virus Neutralizing Antibody that Recognizes a Cryptic Epitope

Ist Teil von

• Structure (London), 2018-01, Vol.26 (1), p.51-59.e4

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Understanding the molecular basis of the neutralizing antibody response to dengue virus (DENV) is an essential component in the design and development of effective vaccines and immunotherapeutics. Here we present the structure of a cross-reactive, neutralizing antibody, 3E31, in complex with domain III (DIII) of the DENV envelope (E) protein and reveal a conserved, temperature-sensitive, cryptic epitope on DIII that is not available in any of the known conformations of E on the dengue virion. We observed that 3E31 inhibits E-mediated membrane fusion, suggesting that the antibody is able to neutralize virus through binding an as-yet uncharacterized intermediate conformation of DENV E and sterically block trimer formation. Finally, we show that, unlike cross-reactive fusion peptide-specific antibodies, 3E31 does not promote antibody-dependent enhancement of infection at sub-neutralizing concentrations. Our results highlight the 3E31 epitope on the E protein DIII as a promising target for immunotherapeutics or vaccine design. [Display omitted] •The antibody 3E31 recognizes a cryptic epitope on the dengue virus E protein•3E31 blocks viral fusion and neutralizes all four dengue virus serotypes•No virus enhancement at sub-neutralizing levels•The epitope represents potential target for safe immunotherapeutic and vaccine design Li et al. reveal the structural basis of the interaction between dengue virus and a neutralizing antibody, 3E31. They show that 3E31 recognizes a temperature-dependent cryptic epitope and demonstrate that 3E31 blocks viral fusion. Their work shows that, unlike many other antibodies, 3E31 does not enhance infection at sub-neutralizing levels.