Pregenomic RNA of HBV is revealed to bind with RIG-1 protein, which induces IFN and ISGs production to prevent HBV infection.206 Moreover, RIG-1 counteracts the interaction of HBV polymerase, thus suppressing viral replication and production.207 HBV covalently closed circular DNA (cccDNA), the transcriptional template for viral RNA, is indispensable for HBV persistence and chronic hepatitis. The gene discussed is RIGI; the disease is chronic hepatitis.