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 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.

SUBMITTER: Fakhriedzwan Idris 

PROVIDER: S-SCDT-10_1038-S44321-025-00311-6 | biostudies-other |

REPOSITORIES: biostudies-other