MafF is an anti-viral host factor that suppresses transcription from Hepatitis B Virus and Epstein Barr Virus promoters

Herein, we report that Maf bZIP transcription factor F (MafF) promotes host defense against infection with Hepatitis B virus (HBV). Suppression of MafF increased HBV pre-genomic RNA in HBV-infected primary hepatocytes. MafF inhibited the binding of the transcriptional activator, HNF-4α, at overlapping recognition sites in HBV core promoter. Mutations introduced at the MafF binding site abolished the physical interaction between MafF and the HBV promoter and counteracted MafF-mediated suppression of HBV replication. MafF expression was induced by IL-1β and TNF-α in an NF-κB-dependent manner. These findings are consistent with the identified induction of MafF expression in chronic HBV patients, notably during the immune clearance phase. Interestingly, MafF also suppressed expression of the trans-activator, BZLF1, that promotes lytic reactivation of Epstein Barr virus (EBV) infection. In conclusion, MafF is a novel anti-viral host factor which is inducible by inflammatory cytokines, and suppresses transcription from the promoters of susceptible DNA viruses.