Fig. 1

Life cycle of HBV and antiviral mechanisms of cellular innate immunity in hepatocyte. During the lifecycle of HBV, nucleic acid (RNA and DNA) can trigger innate immune system sensors (cGAS/STING, TLRs, or RIG-I) which then initiate a cascade of antiviral signaling. As a result, STATs and IRFs enter into nucleus to promote the transcription of effector genes. The most important effector proteins, IFNs, are secreted out of the cell and bind to receptors (IFNRs) on the cell surface, which then drive hundreds of ISGs to target multiple steps in the lifecycle of HBV. APOBEC3 family members activated by lym. NPC Nuclear pore complex, NTCP sodium taurocholate cotransporting polypeptide, HSPG hepatocyte-associated heparan sulfate proteoglycans, cccDNA covalently closed circular DNA, pgRNA pregenomic RNA, Pol HBV polymerase, HBs(L/M/S) HBV surface antigen (large, middle, small), HBc HBV core antigen, HBx HBV x protein, HBe HBV e antigen, NAs nucleotide analogs, IFN interferon, ISGs IFN stimulated genes, TLRs toll like receptors, RIG-I retinoic acid inducible gene I, MAD5 Melanoma differentiation-associated protein 5, cGAS cyclic GMP–AMP synthase, STING Stimulator of interferon genes. (+) stands for “activation”. (Figure created with BioRender (https://biorender.com))