Significance The cap structure present at the 5′ end of eukaryotic messenger RNAs (mRNAs) regulates RNA stability, translation, and marks mRNA as self, thereby impeding recognition by the innate immune system. Cellular transcripts beginning with adenosine are additionally modified at the N6 position of the 2’-O methylated cap-proximal residue by the methyltransferase PCIF1 to m ⁷ Gpppm ⁶ A _m . We define a function for this N6-adenosine methylation in attenuating the interferon-β–mediated suppression of viral infection. Cells lacking PCIF1, or defective in its enzymatic activity, augment the cell-intrinsic suppressive effect of interferon-β treatment on vesicular stomatitis virus (VSV) and rabies virus (RABV) gene expression. VSV and RABV mRNAs are efficiently methylated by PCIF1, suggesting this contributes to viral evasion of innate immune suppression.