A group of infection-enhancing and focus size-reducing monoclonal antibodies recognized an ‘a and c’ strands epitope in the pr domain of Dengue Virus prM
3
Issued Date
2023-01-02
Resource Type
ISSN
01681702
eISSN
18727492
Scopus ID
2-s2.0-85145556605
Pubmed ID
36455752
Journal Title
Virus Research
Volume
323
Rights Holder(s)
SCOPUS
Bibliographic Citation
Virus Research Vol.323 (2023)
Suggested Citation
Keelapang P., Supasa P., Sriburi R., Puttikhunt C., Cardosa J., Kasinrerk W., Malasit P., Sittisombut N. A group of infection-enhancing and focus size-reducing monoclonal antibodies recognized an ‘a and c’ strands epitope in the pr domain of Dengue Virus prM. Virus Research Vol.323 (2023). doi:10.1016/j.virusres.2022.199015 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81955
Title
A group of infection-enhancing and focus size-reducing monoclonal antibodies recognized an ‘a and c’ strands epitope in the pr domain of Dengue Virus prM
Other Contributor(s)
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 Fcγ 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 ‘a’ strand and ‘c' strand of pr domain. These findings suggest that the pr ‘a and c' strands region is the major binding site of these unusual focus size-reducing anti-prM antibodies.