(A) (i) PARP13 co-factor Trim25 ubiquinates both PARP13 and RIG-I to promote antiviral activity; (ii) PARP13 has high affinity for RNA viruses rich in CpG dinucleotides; (iii) PARP13 promotes ubiquitination, and degradation of influenza protein PB2 (and also PA, not shown), which is blocked by competition from influenza protein PB1 for PARP13 binding. (B) PARP14 is required for enhancing IFN production in response to CoV infection (MHV) or poly(I:C) treatment; meanwhile, coronavirus macrodomain prevents the antiviral effect of PARP14 by removing ADP-ribose from target protein. Created with BioRender.com.