In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 5 ( 2022-5-26), p. e0266136-
Abstract:
Non-structural protein 1 (NS1) is a glycoprotein component of dengue virus (DENV) that is essential for viral replication, infection and immune evasion. Immunization with NS1 has been shown to elicit antibody-mediated immune responses which protect mice against DENV infections. Here, we obtained peripheral blood mononuclear cells from human subjects with secondary dengue infections, which were used to construct a dengue immune phage library displaying single-chain variable fragments. Phage selective for DENV NS1 were obtained by biopanning. Twenty-one monoclonal antibodies (mAbs) against DENV NS1 were generated from the selected phage and characterized in detail. We found most anti-NS1 mAbs used IGHV1 heavy chain antibody genes. The mAbs were classified into strongly and weakly-reactive groups based on their binding to NS1 expressed in dengue virus 2 (DENV2)-infected cells. Antibody binding experiments with recombinant NS1 proteins revealed that the mAbs recognize conformational epitopes on the β-ladder domain (amino acid residues 178–273) of DENV NS1. Epitope mapping studies on alanine-substituted NS1 proteins identified distinct but overlapping epitopes. Protruding amino acids distributed around the spaghetti loop are required for the binding of the strongly-reactive mAbs, whereas the recognition residues of the weakly-reactive mAbs are likely to be located in inaccessible sites facing toward the cell membrane. This information could guide the design of an NS1 epitope-based vaccine that targets cross-reactive conserved epitopes on cell surface-associated DENV NS1.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0266136
DOI:
10.1371/journal.pone.0266136.g001
DOI:
10.1371/journal.pone.0266136.g002
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10.1371/journal.pone.0266136.g003
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10.1371/journal.pone.0266136.g004
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10.1371/journal.pone.0266136.g005
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10.1371/journal.pone.0266136.g006
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10.1371/journal.pone.0266136.t001
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10.1371/journal.pone.0266136.t002
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10.1371/journal.pone.0266136.s001
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10.1371/journal.pone.0266136.s002
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10.1371/journal.pone.0266136.s003
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10.1371/journal.pone.0266136.s004
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10.1371/journal.pone.0266136.s005
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10.1371/journal.pone.0266136.s006
DOI:
10.1371/journal.pone.0266136.s007
DOI:
10.1371/journal.pone.0266136.s008
DOI:
10.1371/journal.pone.0266136.s009
DOI:
10.1371/journal.pone.0266136.s010
DOI:
10.1371/journal.pone.0266136.s011
DOI:
10.1371/journal.pone.0266136.s012
DOI:
10.1371/journal.pone.0266136.s013
DOI:
10.1371/journal.pone.0266136.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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