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131 Results Found

  • Feature Paper
  • Review
  • Open Access
170 Citations
14,895 Views
12 Pages

The Role of cccDNA in HBV Maintenance

  • Lena Allweiss and
  • Maura Dandri

21 June 2017

Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mec...

  • Review
  • Open Access
101 Citations
16,762 Views
19 Pages

27 July 2021

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes...

  • Review
  • Open Access
30 Citations
6,115 Views
22 Pages

Gene Editing Technologies to Target HBV cccDNA

  • Maria Guadalupe Martinez,
  • Elena Smekalova,
  • Emmanuel Combe,
  • Francine Gregoire,
  • Fabien Zoulim and
  • Barbara Testoni

28 November 2022

Hepatitis B virus (HBV) remains a significant cause of mortality and morbidity worldwide, since chronic HBV infection is associated with elevated risk of cirrhosis and hepatocellular carcinoma. Current licensed therapies against HBV efficiently suppr...

  • Review
  • Open Access
79 Citations
16,190 Views
25 Pages

22 May 2017

Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yie...

  • Review
  • Open Access
10 Citations
5,869 Views
15 Pages

Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B

  • Wei He,
  • Zhijin Zheng,
  • Qian Zhao,
  • Renxia Zhang and
  • Hui Zheng

13 December 2024

Chronic hepatitis B (CHB) caused by HBV infection has brought suffering to numerous people. Due to the stable existence of HBV cccDNA, the original template for HBV replication, chronic hepatitis B (CHB) is difficult to cure completely. Despite curre...

  • Review
  • Open Access
20 Citations
8,041 Views
11 Pages

15 April 2024

Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the Hepadnavirida...

  • Article
  • Open Access
17 Citations
5,327 Views
16 Pages

Replenishment of Hepatitis B Virus cccDNA Pool Is Restricted by Baseline Expression of Host Restriction Factors In Vitro

  • Sergey Brezgin,
  • Anastasiia Kostyusheva,
  • Ekaterina Bayurova,
  • Ilya Gordeychuk,
  • Maria Isaguliants,
  • Irina Goptar,
  • Anastasiia Nikiforova,
  • Valery Smirnov,
  • Elena Volchkova and
  • Vladimir Chulanov
  • + 2 authors

Background: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence in patients with chronic HBV infection. Understanding the mechanisms underlying stability and persistence of HBV cccDNA in hepatocy...

  • Article
  • Open Access
1 Citations
1,527 Views
21 Pages

Wnt/β-Catenin Signaling Regulates Hepatitis B Virus cccDNA Levels

  • Atsuya Ishida,
  • Sadahiro Iwabuchi,
  • Ying-Yi Li,
  • Kazuhisa Murai,
  • Takayoshi Shirasaki,
  • Kazuyuki Kuroki,
  • Tetsuro Shimakami,
  • Koki Nio,
  • Kazunori Kawaguchi and
  • Shinichi Hashimoto
  • + 7 authors

Hepatitis B virus (HBV) specifically infects hepatocytes and has a complex life cycle owing to the stabilization and pooling of covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. We previously reported that the suppressio...

  • Article
  • Open Access
15 Citations
3,812 Views
15 Pages

Inflammatory Gene Expression Associates with Hepatitis B Virus cccDNA- but Not Integrant-Derived Transcripts in HBeAg Negative Disease

  • Andrea Magri,
  • James M. Harris,
  • Valentina D’Arienzo,
  • Rosalba Minisini,
  • Frank Jühling,
  • Peter A. C. Wing,
  • Rachele Rapetti,
  • Monica Leutner,
  • Barbara Testoni and
  • Jane A. McKeating
  • + 4 authors

17 May 2022

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (ccc...

  • Article
  • Open Access
2 Citations
2,499 Views
32 Pages

Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA

  • Christine I. Wooddell,
  • Dean Sanders,
  • Zhao Xu,
  • Lung-Yi Mak,
  • Thomas Schluep,
  • Wai-Kay Seto,
  • Bruce D. Given and
  • Man-Fung Yuen

19 December 2024

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts...

  • Article
  • Open Access
3 Citations
3,033 Views
19 Pages

cccDNA-Targeted Drug Screen Reveals a Class of Antihistamines as Suppressors of HBV Genome Levels

  • Ee Chee Ren,
  • Nicole Ziyi Zhuo,
  • Zhi Yi Goh,
  • Isabelle Bonne,
  • Benoît Malleret and
  • Hui Ling Ko

24 September 2023

Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro c...

  • Review
  • Open Access
19 Citations
11,897 Views
14 Pages

4 January 2025

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 nucl...

  • Article
  • Open Access
6 Citations
9,548 Views
23 Pages

An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV

  • Khanit Sa-ngiamsuntorn,
  • Piyanoot Thongsri,
  • Yongyut Pewkliang,
  • Adisak Wongkajornsilp,
  • Pattida Kongsomboonchoke,
  • Phichaya Suthivanich,
  • Suparerk Borwornpinyo and
  • Suradej Hongeng

16 October 2019

More than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventio...

  • Review
  • Open Access
15 Citations
5,136 Views
31 Pages

25 November 2023

There has been over half a century since the discovery of hepatitis B virus (HBV) to now, but approximately 300 million patients with chronic hepatitis B (CHB) still live in the world, resulting in about one million deaths every year. Although curren...

  • Review
  • Open Access
41 Citations
11,339 Views
18 Pages

Mapping the Interactions of HBV cccDNA with Host Factors

  • Nur K. Mohd-Ismail,
  • Zijie Lim,
  • Jayantha Gunaratne and
  • Yee-Joo Tan

1 September 2019

Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has reduced new infections, a cure for chronic hepatitis B (CHB) is still unavailabl...

  • Review
  • Open Access
8 Citations
5,808 Views
19 Pages

Eradication of cccDNA is an ideal goal of chronic hepatitis B (CHB) therapy. Understanding the changes in the cccDNA pool during therapy provides a basis for developing CHB treatment strategies. On the other hand, the shift in the balance of the cccD...

  • Review
  • Open Access
60 Citations
13,849 Views
19 Pages

Detection of HBV Covalently Closed Circular DNA

  • Xiaoling Li,
  • Jinghua Zhao,
  • Quan Yuan and
  • Ningshao Xia

6 June 2017

Chronic hepatitis B virus (HBV) infection affects approximately 240 million people worldwide and remains a serious public health concern because its complete cure is impossible with current treatments. Covalently closed circular DNA (cccDNA) in the n...

  • Communication
  • Open Access
2,296 Views
9 Pages

Chronic Hepatitis B Genotype C Mouse Model with Persistent Covalently Closed Circular DNA

  • Deok-Hwa Seo,
  • Wonhee Hur,
  • Juhee Won,
  • Ji-Won Han,
  • Seung-Kew Yoon,
  • Songmee Bae,
  • Kyun-Hwan Kim and
  • Pil-Soo Sung

7 December 2024

Hepatitis B virus (HBV) can cause chronic infections, significantly increasing the risk of death from cirrhosis and hepatocellular carcinoma (HCC). A key player in chronic HBV infection is covalently closed circular DNA (cccDNA), a stable episomal fo...

  • Review
  • Open Access
23 Citations
5,700 Views
11 Pages

28 February 2023

Hepatitis B virus (HBV) relies on the core protein (HBc) to establish productive infection, as defined by the formation of the covalently closed circularized DNA (cccDNA), as well as to carry out almost every step of the lifecycle following cccDNA fo...

  • Article
  • Open Access
6 Citations
3,749 Views
16 Pages

Super-Resolution Microscopy Analysis of Hepatitis B Viral cccDNA and Host Factors

  • Phuong Thi Bich Doan,
  • Kouki Nio,
  • Tetsuro Shimakami,
  • Kazuyuki Kuroki,
  • Ying-Yi Li,
  • Saiho Sugimoto,
  • Hideo Takayama,
  • Hikari Okada,
  • Shuichi Kaneko and
  • Taro Yamashita
  • + 1 author

16 May 2023

Infection with hepatitis B virus (HBV) cannot be cured completely because of the persistence of covalently closed circular DNA (cccDNA). We previously found that the host gene dedicator of cytokinesis 11 (DOCK11) was required for HBV persistence. In...

  • Review
  • Open Access
18 Citations
4,164 Views
14 Pages

Hepatitis B Core-Related Antigen as Surrogate Biomarker of Intrahepatic Hepatitis B Virus Covalently-Closed-Circular DNA in Patients with Chronic Hepatitis B: A Meta-Analysis

  • Gian Paolo Caviglia,
  • Angelo Armandi,
  • Chiara Rosso,
  • Davide Giuseppe Ribaldone,
  • Rinaldo Pellicano and
  • Sharmila Fagoonee

Hepatitis B virus (HBV) covalently-closed-circular (ccc)DNA is the key molecule responsible for viral persistence within infected hepatocytes. The evaluation of HBV cccDNA is crucial for the management of patients with chronic HBV infection and for t...

  • Review
  • Open Access
68 Citations
11,942 Views
15 Pages

Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?

  • Kristie Bloom,
  • Mohube Betty Maepa,
  • Abdullah Ely and
  • Patrick Arbuthnot

12 April 2018

Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular...

  • Review
  • Open Access
34 Citations
15,307 Views
14 Pages

26 April 2021

Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments e...

  • Review
  • Open Access
73 Citations
10,357 Views
29 Pages

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

  • Kristi L. Turton,
  • Vanessa Meier-Stephenson,
  • Maulik D. Badmalia,
  • Carla S. Coffin and
  • Trushar R. Patel

30 January 2020

The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently...

  • Article
  • Open Access
544 Views
16 Pages

Development of a Sensitive and Specific RPA-CRISPR/Cas12a Assay for Intrahepatic Quantification of HBV cccDNA

  • Pattida Kongsomboonchoke,
  • Chaiyaboot Ariyachet,
  • Pornchai Kaewsapsak,
  • Pongserath Sirichindakul and
  • Pisit Tangkijvanich

Hepatitis B virus (HBV) persists in infected hepatocytes through covalently closed circular DNA (cccDNA), a stable episomal form that serves as the transcriptional template for viral replication. Accurate and sensitive quantification of intrahepatic...

  • Review
  • Open Access
9 Citations
5,792 Views
25 Pages

Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics

  • Anuj Kumar,
  • Emmanuel Combe,
  • Léa Mougené,
  • Fabien Zoulim and
  • Barbara Testoni

2 October 2024

Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintain...

  • Review
  • Open Access
4 Citations
3,099 Views
12 Pages

8 May 2024

HBV infection is challenging to cure due to the persistence of viral covalently closed circular viral DNA (cccDNA). The dedicator of cytokinesis 11 (DOCK11) is recognized as a guanine nucleotide exchange factor (GEF) for CDC42 that has been reported...

  • Commentary
  • Open Access
1 Citations
1,021 Views
14 Pages

Virological Insights from ARC-520 siRNA and Entecavir Treated Chronically HBV-Infected Patients and Chimpanzees

  • Christine I. Wooddell,
  • Lung Yi Mak,
  • Wai-Kay Seto,
  • Bruce D. Given and
  • Man-Fung Yuen

In a previous study, eight chronically HBV-infected nucleos (t)ide analog (NA)-naïve patients began receiving entecavir (ETV) concomitant with a single ARC-520 HBV siRNA injection. This single dose of ARC-520 (SD) was followed by 6–8 month...

  • Article
  • Open Access
2 Citations
2,113 Views
19 Pages

Lipid Nanoparticle-Encapsulated TALEN-Encoding mRNA Inactivates Hepatitis B Virus Replication in Cultured Cells and Transgenic Mice

  • Tiffany Smith,
  • Prashika Singh,
  • Ridhwaanah Bhana,
  • Dylan Kairuz,
  • Kristie Bloom,
  • Mohube Betty Maepa,
  • Abdullah Ely and
  • Patrick Arbuthnot

7 August 2025

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely...

  • Review
  • Open Access
3 Citations
3,179 Views
15 Pages

Co-Transcriptional Regulation of HBV Replication: RNA Quality Also Matters

  • Guillaume Giraud,
  • Khadija El Achi,
  • Fabien Zoulim and
  • Barbara Testoni

16 April 2024

Chronic hepatitis B (CHB) virus infection is a major public health burden and the leading cause of hepatocellular carcinoma. Despite the efficacy of current treatments, hepatitis B virus (HBV) cannot be fully eradicated due to the persistence of its...

  • Review
  • Open Access
35 Citations
12,898 Views
19 Pages

The hepatitis B virus (HBV) cannot be removed completely from infected hepatocytes, owing to the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HC...

  • Review
  • Open Access
5 Citations
3,358 Views
18 Pages

25 October 2024

Cells have developed various mechanisms to counteract viral infections. In an evolutionary arms race, cells mobilize cellular restriction factors to fight off viruses, targeted by viral factors to facilitate their own replication. The hepatitis B vir...

  • Review
  • Open Access
7 Citations
2,292 Views
19 Pages

Human viral infections remain a significant global health challenge, contributing to a substantial number of cancer cases worldwide. Among them, infections with oncoviruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are key drivers o...

  • Review
  • Open Access
7 Citations
10,654 Views
10 Pages

26 August 2021

Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating co...

  • Review
  • Open Access
39 Citations
10,152 Views
8 Pages

Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6

  • Christine M. Livingston,
  • Dhivya Ramakrishnan,
  • Michel Strubin,
  • Simon P. Fletcher and
  • Rudolf K. Beran

3 April 2017

Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DN...

  • Article
  • Open Access
10 Citations
2,707 Views
16 Pages

The Hepatitis B virus (HBV) HBx and HBc proteins play a crucial role in associating with covalently closed circular DNA (cccDNA), the primary factor contributing to intrahepatic viral persistence and a major obstacle in achieving a cure for HBV. The...

  • Review
  • Open Access
29 Citations
12,705 Views
18 Pages

19 October 2017

Hepatitis B virus (HBV) is a major etiologic agent of acute and chronic hepatitis, and end-stage liver disease. Establishment of HBV infection, progression to persistency and pathogenesis are determined by viral and cellular factors, some of which re...

  • Review
  • Open Access
275 Views
25 Pages

31 January 2026

Hepatitis B virus (HBV) pregenomic RNA (pgRNA), transcribed directly from nuclear covalently closed circular DNA (cccDNA), is an essential component in viral replication. The synthesis and encapsidation of pgRNA depend significantly on the transcript...

  • Review
  • Open Access
62 Citations
8,906 Views
20 Pages

Advances with RNAi-Based Therapy for Hepatitis B Virus Infection

  • Fiona van den Berg,
  • Shonisani Wendy Limani,
  • Njabulo Mnyandu,
  • Mohube Betty Maepa,
  • Abdullah Ely and
  • Patrick Arbuthnot

4 August 2020

Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an...

  • Review
  • Open Access
24 Citations
5,461 Views
17 Pages

Hepatitis B Core-Related Antigen and New Therapies for Hepatitis B

  • Takehisa Watanabe,
  • Takako Inoue and
  • Yasuhito Tanaka

The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDN...

  • Review
  • Open Access
60 Citations
11,122 Views
23 Pages

New Approaches to the Treatment of Chronic Hepatitis B

  • Alexandra Alexopoulou,
  • Larisa Vasilieva and
  • Peter Karayiannis

1 October 2020

The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg lo...

  • Article
  • Open Access
13 Citations
8,539 Views
13 Pages

Comprehensive Analysis of Hepatitis B Virus Promoter Region Mutations

  • Vanessa Meier-Stephenson,
  • William T. R. Bremner,
  • Chimone S. Dalton,
  • Guido Van Marle,
  • Carla S. Coffin and
  • Trushar R. Patel

1 November 2018

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists, due, in part, to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides...

  • Article
  • Open Access
514 Views
18 Pages

Development of a Novel Human Hepatoma Cell Line Supporting the Replication of a Recombinant HBV Genome with a Reporter Gene

  • Shotaro Kawase,
  • Tetsuro Shimakami,
  • Kazuyuki Kuroki,
  • Kazuhisa Murai,
  • Masaya Funaki,
  • Mika Yoshita,
  • Masaki Kakuya,
  • Reo Suzuki,
  • Ying-Yi Li and
  • Taro Yamashita
  • + 7 authors

30 January 2026

Hepatitis B virus (HBV) remains a major global health threat because covalently closed circular DNA (cccDNA) persists in hepatocytes and limits the efficacy of current antiviral therapies. Effective HBV research and drug screening require culture mod...

  • Review
  • Open Access
4 Citations
4,060 Views
28 Pages

Recent Advances in the Development of Sulfamoyl-Based Hepatitis B Virus Nucleocapsid Assembly Modulators

  • Sandesha Nayak,
  • Jayaraj Gowda,
  • Syed Azeem Abbas,
  • Hyejin Kim and
  • Soo Bong Han

30 November 2023

Hepatitis B virus (HBV) is the primary contributor to severe liver ailments, encompassing conditions such as cirrhosis and hepatocellular carcinoma. Globally, 257 million people are affected by HBV annually and 887,000 deaths are attributed to it, re...

  • Review
  • Open Access
1 Citations
3,917 Views
18 Pages

Chronic Hepatitis B: Current Management and Future Directions

  • Hamza Ertugrul,
  • Esra Ekiz,
  • Sibel Islak Mutcali,
  • Veysel Tahan and
  • Ebubekir Daglilar

23 September 2025

Chronic hepatitis B virus (HBV) infection remains a major global health burden, affecting millions and contributing significantly to liver-related morbidity and mortality. While substantial progress has been made in elucidating the virology and natur...

  • Review
  • Open Access
6 Citations
5,978 Views
26 Pages

Imaging of Hepatitis B Virus Nucleic Acids: Current Advances and Challenges

  • Luisa F. Bustamante-Jaramillo,
  • Joshua Fingal,
  • Marie-Lise Blondot,
  • Gustaf E. Rydell and
  • Michael Kann

8 March 2022

Hepatitis B virus infections are the main reason for hepatocellular carcinoma development. Current treatment reduces the viral load but rarely leads to virus elimination. Despite its medical importance, little is known about infection dynamics on the...

  • Review
  • Open Access
41 Citations
16,123 Views
10 Pages

Application of CRISPR/Cas9 Technology to HBV

  • Guigao Lin,
  • Kuo Zhang and
  • Jinming Li

2 November 2015

More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target th...

  • Review
  • Open Access
7 Citations
3,581 Views
17 Pages

Evaluation of Interfering RNA Efficacy in Treating Hepatitis B: Is It Promising?

  • Giovana Paula Angelice,
  • Pedro Henrique Roque,
  • Gabriel Valente,
  • Krishna Galvão,
  • Livia Melo Villar,
  • Vinicius Motta Mello,
  • Francisco C. A. Mello and
  • Bárbara Vieira Lago

31 October 2024

Background: Despite an existing safe and effective vaccine for hepatitis B virus (HBV), it is still a major public health concern. Nowadays, several drugs are used to treat chronic hepatitis B; however, full healing remains controversial. The viral c...

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