In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2021-2-23), p. e1009331-
Abstract:
Different strains within a dengue serotype (DENV1-4) can have smooth, or “bumpy” surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009331
DOI:
10.1371/journal.ppat.1009331.g001
DOI:
10.1371/journal.ppat.1009331.g002
DOI:
10.1371/journal.ppat.1009331.g003
DOI:
10.1371/journal.ppat.1009331.g004
DOI:
10.1371/journal.ppat.1009331.g005
DOI:
10.1371/journal.ppat.1009331.g006
DOI:
10.1371/journal.ppat.1009331.g007
DOI:
10.1371/journal.ppat.1009331.t001
DOI:
10.1371/journal.ppat.1009331.s001
DOI:
10.1371/journal.ppat.1009331.s002
DOI:
10.1371/journal.ppat.1009331.s003
DOI:
10.1371/journal.ppat.1009331.s004
DOI:
10.1371/journal.ppat.1009331.s005
DOI:
10.1371/journal.ppat.1009331.s006
DOI:
10.1371/journal.ppat.1009331.s007
DOI:
10.1371/journal.ppat.1009331.s008
DOI:
10.1371/journal.ppat.1009331.s009
DOI:
10.1371/journal.ppat.1009331.s010
DOI:
10.1371/journal.ppat.1009331.s011
DOI:
10.1371/journal.ppat.1009331.s012
DOI:
10.1371/journal.ppat.1009331.s013
DOI:
10.1371/journal.ppat.1009331.r001
DOI:
10.1371/journal.ppat.1009331.r002
DOI:
10.1371/journal.ppat.1009331.r003
DOI:
10.1371/journal.ppat.1009331.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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