Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Figure 2 Hepatitis delta virus lifecycle. Viral entry is mediated (like hepatitis B virus) 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. Following uncoating, the ribonucleoprotein (RNP) complex consisting of negative-sense single-stranded RNA genome plus the small and large hepatitis delta virus (HDV) antigens (L-HDAg/S-HDAg) are transported to the nucleus. Within the nucleolus, HDV RNA is replicated using a double rolling circle amplification to form the positive-sense anti-genomic RNA and more genomic RNA. From the amplification process, the genomic RNA is transported out of the nucleolus and into the nucleus where it can be transcribed to produce the S-HDAg transcript or undergo A to I editing by ADARI to produce the L-HDAg RNA. Once the RNA transcripts are exported out of the nucleus, translation machinery produces the S-HDAg and L-HDAg which associate with the genomic HDV RNA to produce the RNP complex. The RNP complex passes through the endoplasmic reticulum and Golgi apparatus to obtain its coat and are then released out of the cell to infect neighboring hepatocytes. ER: Endoplasmic reticulum; NTCP: Sodium-taurocholate co-transporting polypeptide; HSPG: Heparin sulfate proteoglycan receptor; RNP: Ribonucleoprotein.