Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach

Figure 1 Hepatitis B virus proteins X and core act on multiple host cell pathways to promote viral persistence. An intricate epigenetic regulatory network is established during Hepatitis B virus infection. Hepatitis B virus proteins X and core contribute to this by either directly or indirectly controlling gene expression, modifying chromatin structure or location, mediating host immune responses, regulating apoptosis, and promoting or preventing ubiquitination. Pathways discussed in ‘Viral factors as epigenetic regulators’ are depicted here. Created with BioRender.com. HBx: Hepatitis B virus X protein; HBc: Hepatitis B virus core protein; IFN: Interferon; IL: Interleukin; NF-κB: nuclear factor-κappa B; PTM: Post-translational modifications; SIRT1: Sirtuin 1; YY1: Yin-Yang 1; HATs: Histone acetyltransferases; HDAC: Histone deacetylase; PCNA: Proliferating cell nuclear antigen; HBXAP: HBx-associated protein; RSF1: Remodeling and spacing factor 1; Par14: Parvulin 14; Par17: Parvulin 17; PP1: Protein phosphatase 1; cAMP: Cyclic adenosine monophosphate; ND10: Nuclear domain 10; GATA2: GATA binding protein 2; ST2: Interleukin 1 receptor-like 1; Th2: T helper cell type 2; Usp15: Ubiquitin-specific peptidase 15; DDB1: Damaged DNA-binding protein 1; Smc5/6: Structural maintenance of chromosomes 5/6; ZEB2: Zinc finger E-box-binding homeobox 2; PSME4: Proteasome activator subunit 4; STIM1: Stromal interaction molecule 1; WDR5: tryptophan-aspartic acid (WD) repeat domain 5 protein; DHX9: DExH-box RNA helicase 9; ub: Ubiquitination; SIRT3: Sirtuin 3; PRMT1: Protein arginine methyltransferase 1; SETDB1: SET domain bifurcated histone lysine methyltransferase 1; HP1: Heterochromatin protein 1 factors; CBP: CREB-binding protein; PCAF: p300/CBP-associated factor; DNMT3a: DNA methyltransferase 3a; MxA: Myxovirus resistance gene A; DR5: Death receptor 5; TRAIL: Tumor necrosis factor-related apoptosis-inducing ligand; E2F1: E2F transcription factor 1; RACK1: Receptor for activated protein kinase C 1.