Loss of pals-22 in C. elegans enhances their resistance to viral and microsporidian pathogens in a pals-25-dependent manner.47 Interestingly, DRH-1 may also activate IPR gene expression independently of RNAi factors, much like mammalian RLR.54,55 Upon viral infection, DRH-1 induces upregulation and nuclear localization of the ZIP-1/bZIP transcription factor, triggering IPR gene expression and antiviral defense (Figure 1A), similar to loss of pals-22. The gene discussed is PRPS1; the disease is viral infectious disease.