A group of infection-enhancing and focus size-reducing monoclonal antibodies recognized an 慳 and c� strands epitope in the pr domain of Dengue Virus prM

Abstract

Partial cleavage of a dengue virus envelope protein prM by furin results in a mixture of extracellular particles with variable levels of maturation and infectivity. Partially mature particles can infect leukocytes via interaction between the prM-anti-prM antibody complex with Fc? receptors. Known prM epitopes involved in antibody-mediated infection are localized to the pr domain. In this study a group of murine anti-prM monoclonal antibodies with strong infection-enhancing activity was found to reduce the focus size of subsets of multiple dengue serotypes that they could enhance. By employing sets of overlapping peptides four antibodies recognizing 2-mercaptoethanol-insensitive epitopes were mapped to a common tetrapeptide located distantly in the b-c loop and furin binding site. Substitution mutations of each or both of the tetrapeptides in virus-like particles however failed to reduce binding. Further mapping experiments were performed using immature virus-like particles with abolished furin binding site to minimize the differential influence of various pr substitutions on pr-M cleavage. Reduction of antibody binding was detected when single alanine substitutions were introduced into the 慳� strand and 慶 strand of pr domain. These findings suggest that the pr 慳 and c strands region is the major binding site of these unusual focus size-reducing anti-prM antibodies. ? 2022 The Authors