Previous studies revealed that MDA5 S828 is phosphorylated by RIO kinase 3 (RIOK3, a protein kinase), which inhibits MDA5 multimerization and keeps this protein in a quiescent condition; however, once virus infection or viral RNA binding occurs, MDA5 is quickly activated via dephosphorylation at S828 by PP1 (39). This evidence concerns the gene RIOK3 and viral infectious disease.