Journal article
Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope
SK Austin, KA Dowd, B Shrestha, CA Nelson, MA Edeling, S Johnson, TC Pierson, MS Diamond, DH Fremont
Plos Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2012
Open access
Abstract
We previously developed a panel of neutralizing monoclonal antibodies against Dengue virus (DENV)-1, of which few exhibited inhibitory activity against all DENV-1 genotypes. This finding is consistent with reports observing variable neutralization of different DENV strains and genotypes using serum from individuals that experienced natural infection or immunization. Herein, we describe the crystal structures of DENV1-E111 bound to a novel CC′ loop epitope on domain III (DIII) of the E protein from two different DENV-1 genotypes. Docking of our structure onto the available cryo-electron microscopy models of DENV virions revealed that the DENV1-E111 epitope was inaccessible, suggesting that th..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was supported in part by the Pediatric Dengue Vaccine Initiative, Burroughs Wellcome Fund, the intramural program of the National Institute of Allergy and Infectious Diseases, and NIH grants R01-AI077955, U01-AI061373, and U54 AI057160 (Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research), and NIAID Contract No. HHSN272200700058C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.