Monoclonal Antibodies That Bind to Domain III of Dengue Virus E Glycoprotein Are the Most Efficient Blockers of Virus Adsorption to Vero Cells

TLDR

The specific mechanisms by which antibodies neutralize flavivirus infectivity are not completely understood. The study investigates how anti‑dengue E‑glycoprotein monoclonal antibodies block virus adsorption to Vero cells to elucidate neutralization mechanisms. The authors examined a defined panel of anti‑DEN E‑glycoprotein monoclonal antibodies for their capacity to inhibit virus adsorption to Vero cells. The study found that most neutralizing MAbs block virus adsorption, with domain III‑specific antibodies being the most potent, indicating that domain III contains the primary receptor‑binding motif of dengue virus.

Abstract

ABSTRACT The specific mechanisms by which antibodies neutralize flavivirus infectivity are not completely understood. To study these mechanisms in more detail, we analyzed the ability of a well-defined set of anti-dengue (DEN) virus E-glycoprotein-specific monoclonal antibodies (MAbs) to block virus adsorption to Vero cells. In contrast to previous studies, the binding sites of these MAbs were localized to one of three structural domains (I, II, and III) in the E glycoprotein. The results indicate that most MAbs that neutralize virus infectivity do so, at least in part, by the blocking of virus adsorption. However, MAbs specific for domain III were the strongest blockers of virus adsorption. These results extend our understanding of the structure-function relationships in the E glycoprotein of DEN virus and provide the first direct evidence that domain III encodes the primary flavivirus receptor-binding motif.