Activation-induced cytidine deaminase (AID) suppresses the activity of HBV EnhII/CP by downregulating FANCE expression.

Activation-induced cytidine deaminase (AID) is a host restriction factor known to suppress hepatitis B virus (HBV) replication. However, the precise mechanisms underlying its antiviral activity remain incompletely understood. Combining RNA-Seq and functional assays, our study reveals a novel pathway by which AID inhibits HBV replication via downregulating the expression of Fanconi anemia complementation group E (FANCE). Our findings demonstrate that AID significantly reduces FANCE expression, and that FANCE promotes viral replication by specifically activating the HBV enhancer II/core promoter (EnhII/CP), a key transcriptional regulatory element. Combinatorial regulation experiments further confirm that FANCE is involved in AID-mediated HBV transcription. These results identify a novel downstream gene of AID, broaden the perspective on the host antiviral immune network against HBV, and provides a rationale for potential antiviral strategies targeting the FANCE regulatory axis.