Characterization of Pathogenic Features of Dengue Virus Serotypes 1–4 in the AG129 Mouse Model

An AG129 mouse infection model with four DENV isolates was established to systematically characterize the early pathogenic phenotypes of these strains. DENV-1 caused 100% mortality by 15 dpi, with sustained viremia, widespread multi-organ injury, and persistent leukopenia. DENV-4 exhibited peak viremia at 4 dpi and unique neurovirulence, presenting exclusive hind-limb paralysis, severe pulmonary hemorrhage, and characteristic cerebral parenchymal lesions. DENV-2 and DENV-3 induced only transient mild viremia and focal tissue alterations without mortality. Hematological and biochemical alterations, as well as occasional splenic hemosiderin deposition, were noted among infected animals. This preclinical dataset offers insights into serotype-specific DENV pathogenesis and may aid future evaluation of broad-spectrum antivirals and tetravalent vaccine candidates.