Glycans on non-structural protein 1 prevent premature T-cell mediated dengue virus clearance.

ABSTRACT: Non-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 wild-type 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

SUBMITTER: Idris F 

PROVIDER: S-EPMC12603335 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature