Associate Professor Helene Minyi Liu's team from the Institute of Biochemistry and Molecular Biology at the Medical School reveals important regulatory mechanisms of MDA5 and the 14-3-3η chaperone protein in antiviral immune responses. This research, recently published in the journal PLOS Pathogens, provides new insights into viral infections and innate immune responses.
The research team discovered that when cells are infected with coronaviruses or enteroviruses, or transfected with high-molecular-weight poly(I) mimicking viral RNA, the receptor MDA5, which detects viral RNA in the cytoplasm, is activated. This activation is facilitated by the 14-3-3η chaperone protein, which helps MDA5 initiate a series of immune responses. The activation of MDA5 simultaneously triggers the activation of Caspase-3, an enzyme crucial for apoptosis. Activated Caspase-3 further leads to the degradation of 14-3-3η protein and the generation of a novel 14-3-3η isoform. This new isoform inhibits MDA5 activation, providing a negative feedback mechanism to shut down MDA5.
This finding is significant as it reveals how viral infections influence dynamic changes in cellular proteins and how the interaction between MDA5 and 14-3-3η balances immune responses. Since excessive or inappropriate immune responses can lead to autoimmune diseases, this research has potential value in developing new therapeutic strategies.
Link to the paper: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012287
Source: https://www.ntu.edu.tw/spotlight/2024/2291_20240814.html
