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PXD065422-1

PXD065422 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGlycans on Non-Structural Protein 1 Prevent Premature T-cell Mediated Dengue Virus Clearance
DescriptionNon-structural protein 1 (NS1) of dengue virus (DENV) harbours two conserved N-glycosylation sites at positions 130 and 207, whose biological roles have remained elusive. Using a clinically relevant mouse model of severe dengue, we showed that DENV that lacked N207 glycans on NS1 was significantly attenuated, and this phenotype was dominant over wildtype virulent DENV. Mice infected with this mutant exhibited accelerated viral clearance, milder lymphopenia and more functional DENV-specific CD8+ T cells. Bulk and single-cell RNA sequencing, cytokine measurements and immune-phenotyping revealed blunted innate inflammatory responses early post-infection, which correlated with reduced PD-L1 expression on innate immune cells and reduced PD-1+ T-cells in mice infected with de-glycosylated DENV. PD-1 blockade demonstrated the involvement of premature T-cell apoptosis through the PD-L1/PD-1 axis in DENV pathogenesis. Collectively our findings support that N207-deglycosylated NS1 inhibits early inflammatory responses, which restricts PD-L1 upregulation on innate immune cells, which in turn limits PD-L1/PD-1 mediated T-cell apoptosis. Our study uncovers a novel immune evasion strategy and identifies PD-L1/PD-1 as a novel mechanism of dengue immunopathogenesis.
HostingRepositoryPRIDE
AnnounceDate2025-11-17
AnnouncementXMLSubmission_2025-11-16_16:08:20.326.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCorrine Wan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-06-25 00:36:03ID requested
12025-11-16 16:08:21announced
Publication List
10.1038/s44321-025-00311-6;
Keyword List
submitter keyword: dengue/glycosylation/PD-1/NS1/T-cell apoptosis.
Contact List
Ian Walah
contact affiliationBiprocessing Technology Institute (BTI), Agency for ScieNce, Technology and Research (A*STAR)
contact emailian_walsh@bti.a-star.edu.sg
lab head
Corrine Wan
contact affiliationBioprocessing technology Institute
contact emailcorrine_wan@bti.a-star.edu.sg
dataset submitter
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Dataset FTP location
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