Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Dengue poses a significant global health challenge with no specific antiviral treatments.
• Studying dengue pathogenesis is hindered by the lack of animal models that accurately mimic human immune responses.
• Conventional NOD-scid IL2R gamma null (NSG) mice have limitations in hematopoiesis for certain cell types.

Purpose of the Study:

• To compare three humanized NOD-derived mouse models for their suitability in studying dengue virus-2 (DENV-2) infection.
• To evaluate the role of human cytokine expression in DENV-2 pathogenesis within these models.

Main Methods:

• Three humanized mouse strains (hu-NSG, hu-EXL, hu-SGM3) were generated by xenotransplanting human CD34+ fetal cord blood cells.
• One strain (hu-SGM3-PBMCs) received human peripheral blood mononuclear cells.
• All models were infected with DENV-2, and viral load, cytokine response, and clinical signs were assessed.

Main Results:

• All humanized mouse models exhibited detectable viremia after DENV-2 infection.
• Mice expressing human cytokines showed higher viremia compared to conventional NSG mice.
• The hu-SGM3-PBMCs model developed lethal infections with significantly increased viremia and clinical symptoms.

Conclusions:

• Humanized NOD-derived mouse models, particularly those expressing human cytokines, are valuable for dengue research.
• These models facilitate the study of dengue pathogenesis and the evaluation of novel antiviral therapies.
• The hu-SGM3-PBMCs model represents a promising platform for investigating severe dengue outcomes.