Regulation of IRFs in EBV lytic and latent infections. (a) Lytic infection. BGLF4 phosphorylates IRF3, but blocks its DNA-binding activity. Zta inhibits IRF7 transcriptional activity and RTA downregulates expression of IRF7 and -3 through unclear mechanisms. LF2 interacts with IRF7 and therefore blocks its dimerization and transcriptional activity. (b) Latency 3. EBV LMP1 induces expression of IRF7, -4, -5 and A20. LMP1 also activates IRF7 through ubiquitination, but A20 inhibits LMP1-stimulated IRF7 ubiquitination and activity. IRF7 induces expression of LMP1 and TAP2, but inhibits BamH I-A rightward transcript (BART) transcript. EBV also induces expression of TLR7 and its downstream target IRF5, and IRF5 inhibits IRF7 through dimerization with IRF7. EBV also induces IRF2 through unknown mechanism.