UC San Diego

The RNA virus infections are harmful for human and animal health as they are highly infectious or lethal. On the other hand, the host cells evolve to possess antiviral mechanism of the innate immune system to fight against the viral infections, which plays a significant role in detecting virus and preventing the progression of infection. The interplay between host cells and virus is complicated and not well understood. The viral invasion and replication can trigger cell lysis, while the self-defense mechanism can induce apoptosis. In this study, we investigated these two different types of cell deaths caused by viral infection (Type I death) or programmed by the cytokine-induced innate antiviral mechanism (Type II death) using time-lapse fluorescence microscopy. Then our study focused on introducing perturbations and mutations to critical components in the innate immune system – the interferon (IFN) pathway, including the cellular IFN⍺ cytokine levels, IFN⍺ receptor 1 (IFNAR1), signal transducer and activator of transcription 1 (STAT1), and retinoic acid-inducible gene I (RIG-I). Our results demonstrated the two types of cell deaths by finding type I cell deaths with significantly higher level of virus than the type II cell deaths. Furthermore, the mutant cell lines exhibited either increased or reduced cluster size and changed cluster characteristics, which suggested that these cytokines and receptors play a pivotal role in driving innate immune responses and triggering type II death. In conclusion, the IFN pathway is indispensable for inducing type II cell death to stop RNA virus infections.