The interplay between the dengue virus and the innate immune response is not fully understood. Here, we use deterministic and stochastic approaches to investigate the dynamics of the interaction between the interferon-mediated innate immune response and the dengue virus. We aim to develop a quantitative representation of these complex interactions and predict their system-level dynamics. Our simulation results predict bimodal and bistable dynamics that represent viral clearance and virus-producing states. Under normal conditions, we determined that the viral infection outcome is modulated by the innate immune response and the positive-strand viral RNA concentration. Additionally, we tested system perturbations by external stimulation, such as the direct induction of the innate immune response by interferon, and a therapeutic intervention consisting of the direct application of mRNA encoding for several interferon-stimulated genes. Our simulation results suggest optimal regimes for the studied intervention approaches.

登革热病毒与先天免疫反应之间的相互作用尚不完全清楚。在这里，我们使用确定性和随机方法来研究干扰素介导的先天免疫应答和登革热病毒之间相互作用的动力学。我们的目标是对这些复杂的相互作用进行定量描述，并预测其系统级动态。我们的模拟结果预测了代表病毒清除率和病毒产生状态的双峰和双稳态动力学。在正常条件下，我们确定病毒感染的结果受先天免疫应答和正链病毒RNA浓度的调节。此外，我们测试了外部刺激对系统的干扰，例如干扰素直接诱导先天免疫反应，以及直接由编码几种干扰素刺激基因的mRNA组成的治疗干预措施。我们的模拟结果为研究的干预方法提出了最佳方案。