Didactic illustration on the topic of HBV-associated Hepatocellular Carcinoma (HCC)
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Figure showing the pathway of HBV virus DNA integration and alteration of hTERT promoter region that are associated with HCC development. In a normal hepatocyte (green cell on the right), as it ages, telomere is shortened gradually due to cell division. If the length of the telomere goes over a critical length, it triggers the cell to undergo apoptosis. 1. In the cancerous hepatocyte (brown cell on the left), the virion of the HBV enters the host cell by binding the NTCP entry receptor on the cell surface. 2. It is enclosed and endocytosed by the endosome. 3. The viral rcDNA is carried to and enters the nucleus through nuclear pore complex. 4. The virus uses host cell DNA repair enzymes to convert rcDNA to cccDNA form. 5. cccDNA acts as the stable templates for viral mRNA transcription including the pgRNA. 6. pgRNA is then translated into rcDNA (major pathway) and dslDNA in the HBV nucleocapsid. 7. In the minor pathway, the 2 enhancers, enhancer I and II in HBV dslDNA causes the upregulation of hTERT proto-oncogene in/near TERT promoter region of Chromosome 5. Telomere formed by the overexpressed telomerase reverse transcriptase is extended beyond the critical length without undergoing a programmed cell death itself. 8. Nuclear dslDNA integrating into the host cell genome also produces high expressions of altered HBx proteins and HBsAg, which will lead to ER and mitochondrial stress responses. 9. Both processes will prevent the cancerous hepatocyte from apoptosis and thus continue the uncontrolled cell replication in the HCC development.
References: 1. Wang, G. & Chen, Z. HBV Genomic Integration and Hepatocellular Carcinoma. Advanced Gut & Microbiome Research. 2022;2022:(1-7). doi:10.1155/2022/2140886. 2. Rizzo, et al. Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses. 2022;14(5):986. doi:10.3390/v14050986.
Drafts and concept development
