Structural basis of differential neutralization of DENV-1 genotypes by an antibody that recognizes a cryptic epitope.
S Kyle Austin, Kimberly A Dowd, Bimmi Shrestha, Christopher A Nelson, Melissa A Edeling, Syd Johnson, Theodore C Pierson, Michael S Diamond, Daved H Fremont
PLoS Pathog | Published : 2012
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..View full abstract
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