In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2022-4-29), p. e1010469-
Abstract:
Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fcγ-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010469
DOI:
10.1371/journal.ppat.1010469.g001
DOI:
10.1371/journal.ppat.1010469.g002
DOI:
10.1371/journal.ppat.1010469.g003
DOI:
10.1371/journal.ppat.1010469.g004
DOI:
10.1371/journal.ppat.1010469.g005
DOI:
10.1371/journal.ppat.1010469.g006
DOI:
10.1371/journal.ppat.1010469.g007
DOI:
10.1371/journal.ppat.1010469.g008
DOI:
10.1371/journal.ppat.1010469.s001
DOI:
10.1371/journal.ppat.1010469.s002
DOI:
10.1371/journal.ppat.1010469.s003
DOI:
10.1371/journal.ppat.1010469.s004
DOI:
10.1371/journal.ppat.1010469.s005
DOI:
10.1371/journal.ppat.1010469.s006
DOI:
10.1371/journal.ppat.1010469.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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