HBV particle entry requires. host receptors hepatocyte-associated. heparin sulphate proteoglycans. (HSPGs) and sodium taurocholate. co-transporting polypeptide. (NTCP). After HBV particle.uncoating, HBV releases relaxed. circular DNA (rcDNA) in. endosomes, rcDNA then.associates with nuclear. pore complex (NPC) to import. into the nucleus. After the translocation, rcDNA. is converted to covalently.closed circular DNA (cccDNA). Then cccDNA is transcribed. to pregenomic RNAs. (pgRNAs) and subgenomic. RNA which act as.both the templates.for reverse transcription.to generate viral DNA. and message RNAs. (mRNAs) for viral protein. translation after export. into the cytoplasm. by associating with. a cellular Tip-associated. protein/nuclear export. factor-1 (TAP/NFX1) and. HBcAg. The pgRNAs. are selectively packaged. inside core particles, and then.followed by P.protein-mediated negative. strand DNA synthesis. After.the degradation.of pgRNAs, the positive. strand DNA is synthesized. to generate rcDNA. At last, HBV.virions are assembled.in the endoplasmic.reticulum (ER)-Golgi compartment. and then released. from the cell. HBV rcDNA. may also return to. the nucleus to repeat. the replication process. producing more cccDNA. (Datta et al., 2012; Ezzikouri et al., 2014) (Fig. 1.2).