Speaker
Description
Positive-sense RNA viruses employ various strategies to suppress host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial for designing effective antiviral strategies. Here, we develop a mathematical model integrating the intracellular viral life cycle with key innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model captures both virus-specific dynamics and innate immune responses driving their coupled behavior. Comparing viruses, we show how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load due to rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control seen in HCV. Our model demonstrates that virus-host interactions exhibit sharp bifurcation behavior, where minor differences in immune strength or viral suppression capacity determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. The model also recapitulates molecular players involved in IFN desensitization and predicts optimal timing and dosing strategies for interferon-based prophylactic therapies. Our approach reveals fundamental features governing the balance between infection establishment and immune control in RNA virus infections.
