HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication
Hepatitis B virus (HBV) is a major global health issue, with an estimated 254 million people living with chronic HBV infection worldwide as of 2022. Chronic HBV infection is the leading cause of cirrhosis and liver cancer. Current treatment with nucleos(t)ide analogs is effective in the suppression...
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MDPI AG
2025-01-01
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| Series: | Biomolecules |
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| author | André Boonstra Gulce Sari |
| author_facet | André Boonstra Gulce Sari |
| author_sort | André Boonstra |
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| description | Hepatitis B virus (HBV) is a major global health issue, with an estimated 254 million people living with chronic HBV infection worldwide as of 2022. Chronic HBV infection is the leading cause of cirrhosis and liver cancer. Current treatment with nucleos(t)ide analogs is effective in the suppression of viral activity but generally requires lifelong treatment. They fail to eradicate the HBV viral reservoir, called covalently closed circular DNA (cccDNA), which replicates in the nucleus of liver cells. The cccDNA serves as the sole template for viral replication, as it generates the pregenomic RNA (pgRNA) necessary for producing new viral genomes. This stable form of viral DNA can reactivate the virus when treatment is stopped. HBV cccDNA is therefore one of the main challenges in curing chronic HBV infections. By targeting steps such as cccDNA formation, capsid assembly, or particle secretion, researchers continue to seek ways to interfere with HBV replication and to reduce its persistence, ultimately to eradicate HBV as a global health problem. This review provides an overview of what is currently known about cccDNA formation and biogenesis and the ongoing efforts to target and eradicate it to cure chronic HBV infections. |
| format | Article |
| id | doaj-art-55abbe9a242c4c33bbf0b00a83d110bd |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-55abbe9a242c4c33bbf0b00a83d110bd2025-01-24T13:25:02ZengMDPI AGBiomolecules2218-273X2025-01-011516210.3390/biom15010062HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral EradicationAndré Boonstra0Gulce Sari1Department of Gastroenterology and Hepatology, Erasmus Medical Center, Wytemaweg 80, 3015CN Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, Wytemaweg 80, 3015CN Rotterdam, The NetherlandsHepatitis B virus (HBV) is a major global health issue, with an estimated 254 million people living with chronic HBV infection worldwide as of 2022. Chronic HBV infection is the leading cause of cirrhosis and liver cancer. Current treatment with nucleos(t)ide analogs is effective in the suppression of viral activity but generally requires lifelong treatment. They fail to eradicate the HBV viral reservoir, called covalently closed circular DNA (cccDNA), which replicates in the nucleus of liver cells. The cccDNA serves as the sole template for viral replication, as it generates the pregenomic RNA (pgRNA) necessary for producing new viral genomes. This stable form of viral DNA can reactivate the virus when treatment is stopped. HBV cccDNA is therefore one of the main challenges in curing chronic HBV infections. By targeting steps such as cccDNA formation, capsid assembly, or particle secretion, researchers continue to seek ways to interfere with HBV replication and to reduce its persistence, ultimately to eradicate HBV as a global health problem. This review provides an overview of what is currently known about cccDNA formation and biogenesis and the ongoing efforts to target and eradicate it to cure chronic HBV infections.https://www.mdpi.com/2218-273X/15/1/62hepatitis Bcovalently closed circular (ccc) DNAviral reservoir |
| spellingShingle | André Boonstra Gulce Sari HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication Biomolecules hepatitis B covalently closed circular (ccc) DNA viral reservoir |
| title | HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication |
| title_full | HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication |
| title_fullStr | HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication |
| title_full_unstemmed | HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication |
| title_short | HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication |
| title_sort | hbv cccdna the molecular reservoir of hepatitis b persistence and challenges to achieve viral eradication |
| topic | hepatitis B covalently closed circular (ccc) DNA viral reservoir |
| url | https://www.mdpi.com/2218-273X/15/1/62 |
| work_keys_str_mv | AT andreboonstra hbvcccdnathemolecularreservoirofhepatitisbpersistenceandchallengestoachieveviraleradication AT gulcesari hbvcccdnathemolecularreservoirofhepatitisbpersistenceandchallengestoachieveviraleradication |