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.
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
Yang Wang, Yumeng Li, Wenjing Zai, Kongying Hu, Yuanfei Zhu, Qiang Deng, Min Wu, Yaming Li, Jieliang Chen, Zhenghong Yuan
Summary: This study examined the impact of epigenetic modifications on the stability and vulnerability of hepatitis B virus covalently closed circular DNA (cccDNA). Results showed that cccDNA significantly decreased during cell division, but varied in transcriptional activity and epigenetic state. cccDNA with low transcriptional activity was found to be more difficult to access by targeted nucleases and antiviral agents.
Article
Virology
Yingshan Chen, Yongxuan Yao, Kaitao Zhao, Canyu Liu, Yifei Yuan, Hao Sun, Dan Huang, Yi Zheng, Yuan Zhou, Jizheng Chen, Yun Wang, Chunchen Wu, Bixiang Zhang, Yujuan Guan, Feng Li, Rongjuan Pei, Xinwen Chen
Summary: In this study, we identified PARP1 as a host factor required for the formation of HBV cccDNA. PARP1 is activated by recognizing rcDNA-like lesions and interacts with other DNA repair proteins to participate in cccDNA formation. This finding may serve as a potential therapeutic target for chronic hepatitis B.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Liudi Tang, Ping An, Qiong Zhao, Cheryl A. A. Winkler, Jinhong Chang, Ju-Tao Guo
Summary: Elimination or functional inactivation of cccDNA minichromosomes is crucial for curing hepatitis B virus (HBV) infection, but the lack of knowledge on the molecular mechanisms hampers the development of antiviral drugs. The study found that a small molecule inhibitor, B02, enhances cccDNA synthesis through a heat shock protein-mediated cellular response.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Ranjit Chauhan, Qilan Li, Molly E. Woodson, Makafui Gasonoo, Marvin J. Meyers, John E. Tavis
Summary: This study focused on addressing limitations in the development of RNase H inhibitors for hepatitis B virus (HBV). Three inhibitors from different chemotypes were tested on HBV-infected cells, showing efficacy in suppressing cccDNA formation and HBV product production. The inhibitors were more effective when added shortly after infection and were non-toxic in primary human hepatocytes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Virology
Robert L. Kruse, Xavier Legras, Mercedes Barzi
Summary: New research has developed a recombinant circular HBV genome (rcccDNA) to mimic cccDNA, showcasing high levels of HBsAg and HBV DNA expression in murine liver. The use of Cre/LoxP technology helped create specific HBx mutant and GFP reporter plasmids for further exploration of cccDNA biology and antiviral strategies.
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.
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
Maria Guadalupe Martinez, Anders Boyd, Emmanuel Combe, Barbara Testoni, Fabien Zoulim
Summary: Current antiviral therapies for chronic hepatitis B can improve patients' quality of life but do not cure infected hepatocytes. Complete HBV cure requires therapies targeting the cccDNA pool directly. New technologies aim to achieve non-cytolytic direct cccDNA targeting for cure.
JOURNAL OF HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jie Wei, Yueyuan Shi, Chunhong Zou, Hongpeng Zhang, Hui Peng, Shilei Wang, Lulu Xia, Yuan Yang, Xiang Zhang, Junye Liu, Hua Zhou, Miao Luo, Ailong Huang, Deqiang Wang
Summary: The study found that Id1 and E2F4 proteins can inhibit the transcription and replication of HBV, while E2F4 can directly bind to cccDNA and activate the transcription of HBV. These findings contribute to a better understanding of the life cycle of HBV and provide clues for the development of novel therapeutic targets against HBV.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
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)
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
Virology
Yuqi Li, Minjing He, Ruijie Gong, Ziteng Wang, Lin Lu, Shu Peng, Zhiyun Duan, Ying Feng, Yi Liu, Bo Gao
Summary: The study demonstrates that FoxO4 can effectively inhibit HBV replication through multiple mechanisms, particularly by interacting with PML to epigenetically suppress cccDNA, which is of great significance for the treatment of chronic hepatitis B.
JOURNAL OF VIROLOGY
(2022)
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)
Article
Multidisciplinary Sciences
Rodrigo Aguilar, Kerrie B. Spencer, Barry Kesner, Noreen F. Rizvi, Maulik D. Badmalia, Tyler Mrozowich, Jonathan D. Mortison, Carlos Rivera, Graham F. Smith, Julja Burchard, Peter J. Dandliker, Trushar R. Patel, Elliott B. Nickbarg, Jeannie T. Lee
Summary: More and more diseases are now being attributed to non-coding RNA, which could be systematically targeted by drug-like compounds to disrupt RNA structure and epigenetic function.
Article
Biochemistry & Molecular Biology
Scott Tersteeg, Tyler Mrozowich, Amy Henrickson, Borries Demeler, Trushar R. Patel
Summary: This study demonstrates that iPPase can be produced in large quantities and high quality using a reasonably generic laboratory facility, and laboratory-purified iPPase is as effective as commercially available iPPase. Our work provides a robust protocol for efficiently producing active iPPase, significantly reducing the financial strain of large-scale RNA production.
BIOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michael H. D'Souza, Tyler Mrozowich, Maulik D. Badmalia, Mitchell Geeraert, Angela Frederickson, Amy Henrickson, Borries Demeler, Michael T. Wolfinger, Trushar R. Patel
Summary: This study investigated the structure of human LincRNA-p21 using various techniques, determining its low-resolution three-dimensional structure and calculating high-resolution models. The study presents a new approach for understanding the structure of long noncoding RNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Biophysics
Kuniaki Nagayama, Trushar Patel, Haruki Nakamura, Lawrence Berliner, Damien Hall
Summary: This article describes the June 2022 installment of the Editors' Roundup feature, which is a collective description of recently published biophysical research. It includes personal recommendations for articles from several journals.
BIOPHYSICAL REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Maulik D. Badmalia, Higor Sette Pereira, M. Quadir Siddiqui, Trushar R. Patel
Summary: Recent studies have shown that long non-coding RNAs (lncRNAs) play crucial roles in genomic maintenance and disease progression. Due to their length, lncRNAs have complex folded structures and interactions with various biomolecules, enabling them to carry out diverse biological functions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Review
Biotechnology & Applied Microbiology
Soumya Deo, L. Kristi Turton, Tajinder Kainth, Ayush Kumar, Hans-Joachim Wieden
Summary: Antimicrobial peptides (AMPs) are immune defense peptides found in animals, insects, and plants, with broad-spectrum antimicrobial activities. The increasing threat of antibiotic resistance has led to a growing interest in AMPs research for their potential as therapeutic alternatives.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Virology
Higor Sette Pereira, Darren L. Gemmill, M. Quadir Siddiqui, Gunjan Vasudeva, Trushar R. Patel
Summary: Monkeypox virus (MPXV) is a DNA virus endemic in West and Central Africa. Recent outbreaks in non-endemic nations have raised concerns, and the availability of effective treatment options is limited. In this study, the authors explored the potential of G-quadruplexes as therapeutic targets. They identified conserved putative quadruplex-forming sequences in MPXV isolates and demonstrated their formation using spectroscopy and scattering techniques. The authors also found that specific G4-binding partners and a small molecule called TMPyP4 interacted with MPXV G-quadruplexes and reduced the expression of MPXV proteins. These findings provide valuable insights for the development of therapeutics.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tyler Mrozowich, Sean M. Park, Maria Waldl, Amy Henrickson, Scott Tersteeg, Corey R. Nelson, Anneke De Klerk, Borries Demeler, Ivo L. Hofacker, Michael T. Wolfinger, Trushar R. Patel
Summary: This study computationally predicts and biophysically validates the long-range RNA-RNA genomic interaction of Japanese encephalitis virus (JEV). The primary driver of this interaction is identified as the conserved cyclization sequence. The research provides a new approach to study viral and human long-non-coding RNA-RNA interactions and determine their binding affinities, which is crucial for designing potential therapeutics.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Darren L. Gemmill, Corey R. Nelson, Maulik D. Badmalia, Higor S. Pereira, Liam Kerr, Michael T. Wolfinger, Trushar R. Patel
Summary: Zika virus (ZIKV) infection remains a global concern, with no effective treatment or vaccine available. This study identified a specific RNA sequence, G-quadruplexes (G4s), in the Zika virus RNA structure that is conserved across all isolates and plays a crucial role in viral replication. The study also found that certain human proteins have a helicase activity that unfolds the G4 structure in the Zika virus RNA. These findings open up possibilities for developing novel Zika virus therapies targeting the G4 region in the 3' terminal region.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Editorial Material
Biophysics
Borries Demeler, Robert Gilbert, Trushar R. Patel
Summary: The 25th International Analytical Ultracentrifugation (AUC) Workshops and Symposium took place in Lethbridge, Canada in July 2022. With 104 attendees, the event showcased the latest advances in AUC and its applications in various disciplines. In addition to AUC, complementary methods such as isothermal titration calorimetry, light scattering, and cryo-electron microscopy were also discussed.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2023)
Meeting Abstract
Biophysics
Darren L. Gemmill, Higor S. Pereira, Maulik D. Badmalia, Corey R. Nelson, Michael T. Wolfinger, Trushar R. Patel
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Natalie Krahn, Jingji Zhang, Sergey Melnikov, Jeffery M. Tharp, Alessandra Villa, Armaan Patel, Rebecca J. Howard, Haben Gabir, Trushar R. Patel, Jorg Stetefeld, Joseph Puglisi, Dieter Soll
Summary: Protein translation is achieved through tRNA aminoacylation and ribosomal elongation. This study explores the tRNA identity elements for a Delta pylSn tRNA(Pyl) and identifies five key elements necessary for MaPylRS activity.
NUCLEIC ACIDS RESEARCH
(2023)
Meeting Abstract
Biophysics
Tyler Mrozowich, Sean M. Park, Michael T. Wolfinger, Trushar R. Patel
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Maulik Badmalia, Vanessa Meier-Stephenson, Gerardo Balderas Figueroa, Simmone D'Souza, Carla Coffin, Trushar R. Patel
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Sean M. Park, Tyler Mrozowich, Michael T. Wolfinger, Trushar R. Patel
BIOPHYSICAL JOURNAL
(2022)
