Dengue virus 2 lacking N153 glycosylation displayed enhanced recognition by neutralizing antibodies
Fibriansah, G.; Ng, T.-S.; Lim, X.-N.; Tan, A. W. K.; Ting, D. H. R.; Screaton, G. R.; Crowe, J. E.; Alonso, S.; Lok, S.-M.
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Deglycosylated (N153Q) dengue virus (DENV) mutant shows attenuated infection in a mouse model, mainly due to its increased antibody susceptibility. This is consistent with the neutralization assay showing human monoclonal antibodies 2D22 and C10 are more potent towards the mutant than the wild-type (WT) virus. Here, we compared the cryoEM structures of WT and mutant viruses complexed with these Fabs (2.7-3.2 [A] resolution). We observed increased occupancies for both Fabs on the mutant virus, suggesting higher accessibility of epitopes that were previously blocked by glycosylation. Using biolayer interferometry, we showed although the Fabs have slower binding rate to the mutant than WT virus, they also have slower dissociation rate. The slow dissociation rate might contribute to higher Fab occupancies, as once bound, they remain associated with the virus. N153Q mutant might be a good vaccine candidate, as important epitopes are made more accessible for stimulating highly potent antibodies.
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