The development of animal models of dengue virus (DENV) infection and\r\ndisease has been challenging, as epidemic DENV does not naturally infect non-human\r\nspecies. Non-human primates (NHPs) can sustain viral replication in relevant cell types\r\nand develop a robust immune response, but they do not develop overt disease. In contrast,\r\ncertain immunodeficient mouse models infected with mouse-adapted DENV strains show\r\nsigns of severe disease similar to the ââ?¬Ë?vascular-leakââ?¬â?¢ syndrome seen in severe dengue in\r\nhumans. Humanized mouse models can sustain DENV replication and show some signs of\r\ndisease, but further development is needed to validate the immune response. Classically,\r\nimmunocompetent mice infected with DENV do not manifest disease or else develop\r\nparalysis when inoculated intracranially; however, a new model using high doses of DENV\r\nhas recently been shown to develop hemorrhagic signs after infection. Overall, each\r\nmodel has its advantages and disadvantages and is differentially suited for studies of\r\ndengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs\r\nand vaccines
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