The Covalently Closed Circular Form of Hepatitis B Virus Genome: Is There Now an End in “Site”?  Timothy M. Block, Ju-Tao Guo  Gastroenterology  Volume 150, Issue 1, Pages 34-36 (January 2016) DOI: 10.1053/j.gastro.2015.11.032 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 Antiviral mechanism of inflammatory cytokines against hepatitis B virus (HBV). HBV infection of a hepatocyte begins by binding of virions to Na+-taurocholate cotransporting polypeptides (NTCP) on the cell surface and delivering nucleocapsids into the cytoplasm. Import of the cytoplasmic nucleocapsid DNA into the nucleus to form covalently closed circular (ccc)DNA, viral RNA transcription, pregenomic (pg) RNA encapsidation, DNA replication in the cytoplasmic nucleocapsids as well as virion assembly and secretion via multivesicle body (MVB) pathway are also depicted. Interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α or lymphotoxin-β (LT-β) bind to their cognate receptors on cell surface to elicit signaling cascades leading to activation of APOBEC3A and/or APOBEC3B gene expression. The APOBEC3 proteins are subsequently recruited to cccDNA, through interaction with HBV capsid proteins, to deaminate the cytidines in the minus-strand of cccDNA. The deamination of cccDNA results in uracil–DNA glycosylase cleavage of uracils to form apurinic/apyrimidinic sites, which are recognized and cleaved by apurinic/apyrimidinic (AP) endonucleases. In addition, IFN-α also induces the expression of other IFN-stimulated genes (ISGs) that inhibit cccDNA transcription and pregenomic pgRNA encapsidation. Gastroenterology 2016 150, 34-36DOI: (10.1053/j.gastro.2015.11.032) Copyright © 2016 AGA Institute Terms and Conditions