Hepatitis Delta Virus and Hepatocellular Carcinoma
<p>Schematic representation of HDV viral particle. Abbreviations: HBsAg (hepatitis B surface antigen); L-HDAg (large-hepatitis delta antigen); S-HDAg (small-hepatitis delta antigen); -ssRNA (negative single-stranded RNA). Created using <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p> "> Figure 2
<p>Life cycle of HDV. (1) The virus binds to the NTCP membrane receptor by the envelope composed of HBV HBsAgs. The viral particle then enters the cell through endocytosis, and the viral ribonucleoprotein is released into the cytoplasm. (2) The L- and S-HDAgs contain a nuclear localization signal that leads to the translocation of the viral ribonucleoprotein into the nucleus. (3) Here, the transcription of HDAg mRNA occurs via recruitment by the cellular RNA polymerase II. The HDAg mRNA is then exported to the cytoplasm, where it is translated to produce S-HDAgs. (4) During the first phase of replication, the HDV genomic RNA serves as a template to produce antigenomic RNA via RNA polymerase I. (5) The antigenomic RNA is then used by RNA polymerase II to produce new genomic RNAs. (6) The antigenomic RNA is also modified by the ADAR1 enzyme, which leads to the elimination of the stop codon of the S-HDAg. (7) The modified antigenomic RNA is replicated into the genomic RNA, thus inducing the transcription of the modified HDAg mRNA, which is exported to the cytoplasm, where this time, it leads to the production of the L-HDAg protein. (8) The L-HDAg contains a prenylation site that is farnesylated by a cellular farnesyltransferase before being translocated to the nucleus. (9) Both forms of the HDAg interact with the newly synthesized genomic RNA to form new viral ribonucleoproteins (RNPs) that are exported to the cytoplasm. (10) The L-HDAg, through its farnesylated cysteine, interacts with the cytosolic part of the HBsAg on the surface of the endoplasmic reticulum, thus inducing viral RNPs envelopment. (11) Enveloped viral particles are subsequently secreted through the endoplasmic reticulum (ER)–Golgi secretory pathway. (12) HDV virions exit the infected cell. The figure represents a cell infected with HBV, represented by the presence of cccDNA and the transcription of mRNA that lead to the translation of the HBsAgs necessary for the formation of the HDV envelope. Created using <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p> "> Figure 3
<p>Schematic representation of the mechanisms by which HDV potentially induces HCC. The main downregulated pathways involved are as follows: hepatic fbrosis and hepatic stellate cell activation, while the most upregulated pathways are: Hedgehog signaling, GADD45, DNA damage-induced 14-3-3σ signaling, cyclins and cell cycle regulation, G2/M DNA damage, checkpoint regulation, and hereditary breast cancer. Created using <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p> ">
Abstract
:1. Introduction
2. Virological Aspects
3. Epidemiology
4. Clinical Outcomes of HDV Infection
5. HDV Pathogenesis
Immunological Aspects
6. HDV and HCC Development: Potential Oncogenic Mechanisms
7. Clinical Features of HDV Infection and HCC Development
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Lombardo, D.; Franzè, M.S.; Caminiti, G.; Pollicino, T. Hepatitis Delta Virus and Hepatocellular Carcinoma. Pathogens 2024, 13, 362. https://doi.org/10.3390/pathogens13050362
Lombardo D, Franzè MS, Caminiti G, Pollicino T. Hepatitis Delta Virus and Hepatocellular Carcinoma. Pathogens. 2024; 13(5):362. https://doi.org/10.3390/pathogens13050362
Chicago/Turabian StyleLombardo, Daniele, Maria Stella Franzè, Giuseppe Caminiti, and Teresa Pollicino. 2024. "Hepatitis Delta Virus and Hepatocellular Carcinoma" Pathogens 13, no. 5: 362. https://doi.org/10.3390/pathogens13050362