Hepatitis B and circadian rhythm of the liver

Figure 1 Hepatitis B virus life cycle. Hepatitis B virus (HBV) enters hepatocytes via interaction with the heparan sulfate proteoglycan (HSPG), followed by the sodium taurocholate co-transporting polypeptide (NTCP) receptor. The virus envelope and the hepatocytes’ membrane merge, releasing the nucleocapsid into the cytoplasm. The viral genome is transferred to the nucleus after the capsid is removed. The relaxed circular genome is restored in the nucleus, resulting in covalently closed circular DNA (cccDNA), and viral DNA could be integrated into the host DNA. Integrated viral DNA is a constant source of hepatitis B surface antigen (dashed line). The cccDNA is a template for pregenomic RNA (pgRNA) production and the transcription of all viral mRNAs. In addition, the cccDNA is associated with host factors and cellular histones, and forms a minichromosome. The core proteins are constructed into nucleocapsids together with pgRNA. Viral polymerase converts the pgRNA to relax circular DNA, resulting in a mature nucleocapsid. The core particles can recycle and replenish cccDNA (dashed line), or gather with the envelope proteins in the endoplasmic reticulum and Golgi, and enter the secretory pathway. Through the secretory process, virions gain surface antigens and are secreted as infectious virions-Dane particles. Also, incomplete subviral particles are secreted, such as spheres and filaments lacking nucleocapsid proteins. HSP: Heparan sulfate proteoglycan; NTCP: Sodium taurocholate co-transporting polypeptide receptor; cccDNA: Covalently closed circular DNA; pgRNA: Pregenomic RNA; HBx: Hepatitis B protein X; HBsAg: Hepatitis B surface antigen; HBe: E antigen; ER: Endoplasmatic reticulum.