Article
Microbiology
Yuan Zhang, Liang Li, Sheng-Tao Cheng, Yi-Ping Qin, Xin He, Fan Li, Dai-Qing Wu, Fang Ren, Hai-Bo Yu, Jing Liu, Juan Chen, Ji-Hua Ren, Zhen-Zhen Zhang
Summary: Hepatitis B virus (HBV) infection is a global public health problem. Current antiviral therapies cannot eradicate chronic hepatitis B (CHB) due to their inability to eliminate intracellular covalently closed circular DNA (cccDNA). Targeting the HBx protein has been shown to inhibit cccDNA transcription and HBV replication. A study found that a drug called rapamycin can inhibit HBV replication by reducing the stability of the HBx protein. This research provides a new strategy for curing CHB.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Maria Guadalupe Martinez, Emmanuel Combe, Aurore Inchauspe, Philippe Emmanuel Mangeot, Elodie Delberghe, Fleur Chapus, Gregory Neveu, Antoine Alam, Kara Carter, Barbara Testoni, Fabien Zoulim
Summary: CRISPR-Cas9 targeting of HBV DNA leads to effective disruption of viral replication and the appearance of episomal HBV DNA variants. Sustainable effects induced by Cas9 post RNP degradation suggest permanent changes in the HBV genome. This study provides insights into the potential of CRISPR-Cas9 as a therapeutic approach for chronic hepatitis B by targeting the viral minichromosome.
Article
Virology
Xupeng Hong, Jianming Hu
Summary: The lysine residues on HBc are not essential for HBV replication, but the K7 coding sequence is critical for HBV RNA production.
JOURNAL OF VIROLOGY
(2022)
Article
Gastroenterology & Hepatology
Xiangying Zhang, Yuan Tian, Ling Xu, Zihao Fan, Yaling Cao, Yingmin Ma, Hao Li, Feng Ren
Summary: A highly sensitive and specific method for detecting HBV cccDNA based on CRISPR-Cas13a technology was established. This method provides a promising alternative for accurate detection of HBV infection, evaluation of antiviral therapy and treatment guidance.
HEPATOLOGY INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Yang Sun, Yan Teng, Liyuan Wang, Zhaoying Zhang, ChaoJia Chen, Yingchun Wang, Xiaodong Zhang, Peng Xiang, Xiaojia Song, Jinghui Lu, Nailin Li, Lifen Gao, Xiaohong Liang, Yuchen Xia, Zhuanchang Wu, Chunhong Ma
Summary: This study identifies LINC01431 as a novel host restriction factor for HBV transcription. It competitively binds with PRMT1 to inhibit the ubiquitination and degradation of PRMT1 mediated by HBx, thus repressing cccDNA transcription. In turn, HBV transcriptionally suppresses LINC01431 expression by inhibiting the transcription factor ZHX2.
Article
Oncology
Chao-Wei Hsu, Yu-De Chu, Ming-Wei Lai, Chih-Lang Lin, Kung-Hao Liang, Yang-Hsiang Lin, Chau-Ting Yeh
Summary: The study developed a PNA-clamping qPCR method to quantify cccDNA with a wider effective range, and found that cccDNA independently predicted overall survival and extrahepatic metastasis in HBV-related hepatocellular carcinoma patients.
Review
Virology
Megan A. Mendenhall, Xupeng Hong, Jianming Hu
Summary: Hepatitis B virus (HBV) relies on the core protein (HBc) for infection and lifecycle. Different effects of HBc on cccDNA formation during de novo infection vs. recycling suggest its critical role in HBV trafficking and nucleocapsid disassembly. Understanding these roles can aid in developing an HBV cure and animal models for research and drug development.
Article
Gastroenterology & Hepatology
Zaichao Xu, Li Zhao, Youquan Zhong, Chengliang Zhu, Kaitao Zhao, Yan Teng, Xiaoming Cheng, Qiang Chen, Yuchen Xia
Summary: This study established a novel mouse model that can generate HBV cccDNA and is responsive to antiviral treatments. This model is of great importance for studying HBV cccDNA and developing new antiviral drugs against HBV infection.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Gang Wang, Jun Guan, Nazif U. Khan, Guojun Li, Junwei Shao, Qihui Zhou, Lichen Xu, Chunhong Huang, Jingwen Deng, Haihong Zhu, Zhi Chen
Summary: This article discusses the use of interferon-alpha and nucleot(s)ide analogs in the treatment of chronic hepatitis B virus infections. While NAs can reduce viral loads, they cannot eliminate covalently-closed-circular DNA (cccDNA), and IFN-alpha may potentially target cccDNA but its clinical effects in eradicating cccDNA in hepatocytes of patients with HBV are not well understood.
Review
Oncology
Xiaodong Zhang, Yufei Wang, Guang Yang
Summary: HBV infections are a global public health concern with the cccDNA template being a key factor in the replication cycle. Host factors involved in HBV cccDNA epigenetic modulation contribute to the development of HCC. The review discusses advances in research on HBV cccDNA, its modulation factors, and potential therapeutic strategies targeting cccDNA. The role of HBx in HBV cccDNA transcription and hepatocarcinogenesis is also highlighted.
CANCER BIOLOGY & MEDICINE
(2022)
Review
Gastroenterology & Hepatology
Zhi Yi Goh, Ee Chee Ren, Hui Ling Ko
Summary: Hepatitis B virus infection remains a major global health threat with existing treatment options unable to fully eradicate the virus, highlighting the need for novel strategies to sustain interferon-mediated antiviral mechanisms. Efforts are focused on understanding how interferons act to eliminate HBV through anti-cccDNA functions and identifying drug targets within the interferon signaling pathway and HBV mechanisms to enhance treatment efficacy.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Microbiology
Elena S. Kim, Jun Zhou, Hu Zhang, Alexander Marchetti, Maarten van de Klundert, Dawei Cai, Xiaoyang Yu, Bidisha Mitra, Yuanjie Liu, Mu Wang, Ulrike Protzer, Haitao Guo
Summary: In this study, researchers identified HMGB1 as a novel host restriction factor of HBV cccDNA with epigenetic silencing mechanism, and demonstrated that the viral protein HBx can counteract HMGB1 and maintain an active state of cccDNA. This study contributes to a better understanding of virus-host interaction during HBV infection and has implications for the development of HBV infection epigenetic drugs and cancer therapeutics strategies.
Review
Biochemistry & Molecular Biology
Yeon-Su Lee, Yong Sun Lee
Summary: nc886 is a medium-sized non-coding RNA transcribed by RNA polymerase III (Pol III) and has diverse roles in tumorigenesis, innate immunity, and other cellular processes. The expression of nc886 is controlled by multiple mechanisms, including promoter CpG DNA methylation and transcription factor activity. Additionally, its RNA instability contributes to its highly variable expression levels. This comprehensive review discusses nc886's variable expression in physiological and pathological conditions and examines the regulatory factors that determine its expression levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Microbiology
Jie-Li Hu, Ai-Long Huang
Summary: Eradication of cccDNA is the ultimate goal of CHB therapy and understanding its dynamics is crucial for the development of treatment strategies. The half-life of cccDNA is not an intrinsic property but is determined by the state and fate of host cells. Factors such as noncytopathic effects and hepatocyte turnover drive cccDNA decay. The review highlights the major factors influencing cccDNA half-life and areas requiring further study.
Article
Virology
Bo Peng, Zhiyi Jing, Zhongmin Zhou, Yinyan Sun, Guilan Guo, Zexi Tan, Yan Diao, Qiyan Yao, Yi Ping, Xuelei Li, Tengfei Ren, Bin Li, Wenhui Li
Summary: This study examines cccDNA transcription at the single-cell level through isolating primary human hepatocytes infected with HBV using 5' end sequencing. The research reveals that infected cells can generate all viral transcripts or only transcripts from the X gene and its associated enhancer I domain. Nonproductive transcription of cccDNA can be activated by incoming virus and cccDNA can be transcribed to produce HBx even in the absence of HBx. These findings shed new light on the mechanism of HBV infection and may contribute to the development of a functional cure for HBV.
JOURNAL OF VIROLOGY
(2023)
