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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Dengue virus infects macrophages and dendritic cells in a mouse model of infection
Jennifer L Kyle1, P Robert Beatty, Eva Harris
1Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
Abstract:
Dengue fever is a mosquitoborne viral illness caused by 4 dengue viruses (DENV-1-4). The cellular tropism of DENV has not been definitively determined, despite its importance for understanding viral pathogenesis and identifying therapeutic targets. To define DENV cellular tropism in a small animal model, 129/Pas mice lacking interferon-alpha/beta and/or-gamma receptors were infected with DENV via a subcutaneous route. During the first week after infection, virus was present in lymph nodes, spleen, bone marrow, and circulating white blood cells. F4/80+CD11b+ macrophages and CD11c+ dendritic cells were demonstrated to be targets for DENV-2 infection in the spleen by flow cytometry directed to structural and nonstructural DENV proteins and by magnetic bead separation followed by strand-specific reverse-transcriptase polymerase chain reaction. We find that the initial cellular tropism of DENV in mice is similar to that reported in humans, thereby paving the way for investigation of cellular tropism and pathogenesis of DENV in primary and secondary infections.
Insights
This study identifies macrophages and dendritic cells as key targets for dengue virus (DENV) infection in mice. This finding helps understand dengue pathogenesis and develop new therapies.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Dengue virus (DENV) causes a significant global health burden.
- Understanding DENV's cellular tropism is crucial for pathogenesis research and therapeutic target identification.
- Previous studies have not definitively determined DENV's cellular targets.
Purpose of the Study:
- To define the cellular tropism of DENV in a small animal model.
- To identify specific immune cells targeted by DENV infection.
- To provide a foundation for further research into DENV pathogenesis.
Main Methods:
- Infection of interferon receptor-deficient mice with DENV.
- Analysis of viral presence in various tissues and blood.
- Flow cytometry and RT-PCR to identify DENV-infected cells in the spleen.
- Magnetic bead separation for cell isolation.
Main Results:
- DENV was detected in lymph nodes, spleen, bone marrow, and white blood cells within the first week post-infection.
- Macrophages (F4/80+CD11b+) and dendritic cells (CD11c+) in the spleen were identified as primary targets for DENV-2 infection.
- The observed cellular tropism in mice mirrors findings reported in human DENV infections.
Conclusions:
- The study successfully defined DENV's initial cellular tropism in a mouse model.
- Macrophages and dendritic cells are key initial cellular targets of DENV.
- This model is suitable for investigating DENV pathogenesis in primary and secondary infections.

