Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Figure 1 Hepatitis B virus life cycle. Viral entry is mediated by low-affinity binding of the Pre-S1 protein to the heparin sulfate proteoglycan receptor, followed by binding to the sodium-taurocholate co-transporting polypeptide to facilitate entry. The nucleocapsid is transported from the cytoplasm to the nucleus where the relaxed circular DNA (rcDNA) genome is converted into the persistent covalently closed circular DNA (cccDNA) form. Viral mRNA is then transcribed from the cccDNA genome and translated at the rough endoplasmic reticulum. The greater than genome length pregenomic RNA is transported to the cytoplasm, encapsidated by the hepatitis B virus core protein and reverse transcribed by the hepatitis B virus polymerase to produce rcDNA or double-stranded linear DNA. The core particles can then obtain their envelope proteins at the endoplasmic reticulum to be excreted out of the cell, or the core particles containing double-stranded linear DNA can relocate into the nucleus and integrate into the host genome, and the rcDNA can be recycled intracellularly to replenish the cccDNA pool.