Optimizing the dengue virus infection mouse model: Comparing different backgrounds and infection route for enhanced stability

Background In recent decades, the global incidence of dengue fever has been steadily increasing, with continuous geographical expansion. Researchers have successfully modeled most clinical symptoms of human dengue fever using interferon type I (IFN‐I) or combined IFN‐I/II receptor knockout mice infected with dengue virus (DENV). However, this model requires further optimization to better support related studies. Methods This study aimed to establish a stable dengue infection model by evaluating the effects of different genetic backgrounds and injection routes on DENV infection in interferon receptor knockout mice. We first infected various strains of interferon receptor‐deficient mice with DENV and compared their susceptibility based on clinical symptoms, viremia levels, organ indices, histopathological findings, and vascular leakage markers. Subsequently, we selected the most susceptible strain to further investigate the impact of different injection methods on infection outcomes. Results We found that BALB/c background mice with type 1 interferon receptor knockout(IFNAR) had the most obvious symptoms. Subsequently, we selected IFNAR−/−BALB/c mice to further explore the effects of different injection methods on dengue virus infection. The results showed that the intraperitoneal injection group had the most severe clinical symptoms, the longest duration of viremia, and the most obvious degree of organ damage. Conclusion Through systematic screening and optimization, we established a robust animal model of dengue virus infection via intraperitoneal injection in IFNAR−/− BALB/c mice. This model offers a valuable tool for future dengue research.