Pathogenicity and transcriptomic resolution in dengue virus serotype 1 infected AGB6 mouse model

Area of Science:

• Virology
• Immunology
• Pathology

Background:

• Dengue viruses (DENV) cause significant global health and economic burdens.
• Lack of suitable small animal models hinders DENV pathogenesis research and therapeutic development.
• Current DENV vaccines, antibodies, and drugs lack effective preclinical evaluation platforms.

Purpose of the Study:

• To analyze the pathogenicity of DENV-1 in interferon receptor-deficient mice (AGB6).
• To establish a small animal model for evaluating DENV therapeutics.
• To investigate DENV-1-induced host responses and identify key inflammatory factors.

Main Methods:

• Intraperitoneal inoculation of DENV-1 into AGB6 mice.
• Monitoring of clinical signs, viremia, and mortality.
• Tissue collection for viral load quantification and histopathology.
• Brain tissue transcriptome sequencing and gene expression analysis (qPCR, ELISA).

Main Results:

• DENV-1 infection in AGB6 mice induced neurological symptoms and 100% mortality at high doses.
• High viral loads were detected in brain tissue, correlating with histopathological changes.
• Transcriptome analysis revealed aberrant pro-inflammatory cytokine expression, implicating IL-6 and IFN-γ.
• Hemorrhage and hemoconcentration were observed in infected mice.

Conclusions:

• AGB6 mice provide a viable small animal model for studying DENV-1 pathogenesis and neuroinvasion.
• The model facilitates the preclinical testing of dengue vaccines, antibodies, and drugs.
• IL-6 and IFN-γ are identified as potential key mediators of the dengue virus-induced inflammatory response.