biostudies-literatureShan CHHS | National Institutes of HealthNCATS NIH HHSNIAID NIH HHSe01002-18https://www.ebi.ac.uk/biostudies/studies/S-EPMC6189489biostudies-literatureUnknown92(21)Dengue virus (DENV) is the most prevalent mosquito-transmitted viral pathogen in humans. The recently licensed dengue vaccine has major weaknesses. Therefore, there is an urgent need to develop improved dengue vaccines. Here, we report a virion assembly-defective DENV as a vaccine platform. DENV containing an amino acid deletion (K188) in nonstructural protein 2A (NS2A) is fully competent in viral RNA replication but is completely defective in virion assembly. When <i>trans</i>-complemented with wild-type NS2A protein, the virion assembly defect could be rescued, generating pseudoinfectious virus (PIV_NS2A) that could initiate single-round infection. The <i>trans</i>-complementation efficiency could be significantly improved through selection for adaptive mutations, leading to hiJournal of virologyUsing a Virion Assembly-Defective Dengue Virus as a Vaccine Approach.PMC6189489AI127744R01 AI127744UL1 TR001439Zou JZust RXie XFink KShi PYAmbrose RShan CZhang BMackenzie JfalseUsing a Virion Assembly-Defective Dengue Virus as a Vaccine Approach.Dengue virus (DENV) is the most prevalent mosquito-transmitted viral pathogen in humans. The recently licensed dengue vaccine has major weaknesses. Therefore, there is an urgent need to develop improved dengue vaccines. Here, we report a virion assembly-defective DENV as a vaccine platform. DENV containing an amino acid deletion (K188) in nonstructural protein 2A (NS2A) is fully competent in viral RNA replication but is completely defective in virion assembly. When <i>trans</i>-complemented with wild-type NS2A protein, the virion assembly defect could be rescued, generating pseudoinfectious virus (PIV_NS2A) that could initiate single-round infection. The <i>trans</i>-complementation efficiency could be significantly improved through selection for adaptive mutations, leading to hi2018-01-01T00:00:00Z2018 Nov2025-04-05T00:11:30.442Z2019-06-06T20:18:21ZS-EPMC61894893011156710.1128/JVI.01002-1810.1128/jvi.01002-18