This unique lethal model uses a non-mouse-adapted strain of DENV serotype 2 (D2Y98P), isolated from a DENV-infected patient in Singapore, which is highly infectious in AG129 mice.
The model provides consistent clinical manifestations of disease similar to those observed in human cases as previously described.
Low dose of virus required to lead to transient asymptomatic infection followed by death a few days after viral clearance, similar to the progression of the disease in humans.
Increased vascular permeability without morphological damage of the capillary endothelium similar to human disease.
Three key pro-inflammatory cytokines implicated in Dengue Hemorrhagic Fever (DHF) are significantly elevated in D2Y98P-infected AG129 mice.
Non-human primates frequently do not exhibit clinical symptoms of the disease thereby limiting their usefulness for product development. Other mouse models of DENV exist but face challenges because most DENV laboratory strains and clinical isolates do not replicate efficiently in mice. Mouse-adapted DENV strains can display higher infectivity but can lead to irrelevant clinical manifestations such as paralysis. Mice deficient in interferon IFN α/β and γ receptors (AG129 mice) have been shown to allow effective replication of DENV.