Article
Microbiology
Ji Xi, Laura Luckenbaugh, Jianming Hu
Summary: Phosphorylation and dephosphorylation of HBc play critical roles in regulating multiple stages of HBV replication. A consensus binding motif for PP2A on HBc has been identified, indicating its importance in modulating CTD phosphorylation and viral persistence. Pharmacological inhibition of PP2A can impact HBc dephosphorylation and enhance viral replication.
Article
Virology
Gaetan Ligat, Eloi R. Verrier, Michael Nassal, Thomas F. Baumert
Summary: Chronic HBV infection is difficult to cure, but targeting host factors to intervene in the viral life cycle may achieve a cure. Current treatments often require long-term use, with risks of drug resistance and side effects, but interferon therapy has a potential for cure.
CURRENT OPINION IN VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Leonid Serebreni, Lisa-Marie Pleyer, Vanja Haberle, Oliver Hendy, Anna Vlasova, Vincent Loubiere, Filip Nemcko, Katharina Bergauer, Elisabeth Roitinger, Karl Mechtler, Alexander Stark
Summary: Different classes of promoters have distinct mechanisms of transcription initiation, resulting in either focused or dispersed initiation patterns.
Article
Genetics & Heredity
Yasuo Ariumi
Summary: Hepatitis B virus (HBV) restricts the retrotransposition of long interspersed element-1 (LINE-1, L1) in a reverse transcriptase (RT)-independent manner, with HBV polymerase (Pol) playing a key role in inhibiting L1 retrotransposition.
Article
Biochemistry & Molecular Biology
Razia Tajwar, Daniel P. Bradley, Nathan L. Ponzar, John E. Tavis
Summary: The structure of the Hepatitis B virus (HBV) protein, which plays a major role in reverse transcription, has been successfully modeled using computational techniques. The protein has four domains and its structure has remained consistent for hundreds of millions of years. This model will advance our understanding of HBV reverse transcription and enable the development of drugs targeting non-active sites.
Article
Biochemistry & Molecular Biology
Juhee Won, Ah Ram Lee, Mehrangiz Dezhbord, Da Rae Lee, Seong Ho Kim, Jong Chul Kim, Soree Park, Nayeon Kim, Byengjune Jae, Kyun-Hwan Kim
Summary: This study reveals that Besifovir (BFV) may serve as an alternative drug for patients with nucleos(t)ide analogues (NAs) resistance in chronic hepatitis B (CHB) infection. LMV and ETV-resistant mutants are not susceptible to BFV, while ADV and TDF-resistant mutants are sensitive to BFV.
Article
Biochemistry & Molecular Biology
Jong Chul Kim, Hye Young Lee, Ah Ram Lee, Mehrangiz Dezhbord, Da Rae Lee, Seong Ho Kim, Juhee Won, Soree Park, Na Yeon Kim, Jae Jin Shin, Sang Gyune Kim, Young Seok Kim, Jeong-Ju Yoo, Kyun-Hwan Kim
Summary: Hepatitis B virus (HBV) infection is a global health problem, and current clinically approved treatments include nucleos(t)ide analogs (NAs) and interferon alpha. However, little is known about the resistance to a newly developed NA, besifovir dipivoxil maleate (BSV). In this study, a case of viral breakthrough in a chronic hepatitis B (CHB) patient after long-term BSV treatment was reported. Analysis of HBV DNA and reverse transcriptase (RT) domain revealed multiple mutations, with rtL180M (M) and rtM204V (V) mutations conferring resistance to BSV in vitro.
Article
Gastroenterology & Hepatology
Yongzhen Liu, Debby Park, Thomas R. Cafiero, Yaron Bram, Vasuretha Chandar, Anna Tseng, Hans P. Gertje, Nicholas A. Crossland, Lishan Su, Robert E. Schwartz, Alexander Ploss
Summary: This study aimed to investigate the differences in HBV replicative capacity, gene expression, and infective capability across different genotypes. Patient-derived HBV infectious clones were used to analyze the replicative capacity and infectivity of different genotypes. The results showed that there were differences in the replicative capacity, gene expression, and infectivity among different genotypes.
Article
Multidisciplinary Sciences
Catherine T. Chia, Andrew T. Bender, Lorraine Lillis, Benjamin P. Sullivan, Coleman D. Martin, Wynn Burke, Charles Landis, David S. Boyle, Jonathan D. Posner
Summary: This study reports a rapid, highly accurate, and minimally instrumented assay for HCV RNA detection using RT-RPA. The assay can detect all HCV genotypes with a limit of detection of 25 copies per reaction for genotype 1. Clinical experiments showed that the RT-RPA assay has a sensitivity and specificity of 100%. The accuracy, short runtime, and low heating demands of RT-RPA make it potentially valuable for point-of-care HCV testing.
Article
Biochemistry & Molecular Biology
Huiming Zhang, Zhaolian Lu, Yu Zhan, Judith Rodriguez, Chen Lu, Yong Xue, Zhenguo Lin
Summary: Regulation of gene expression starts from transcription initiation, which is critical for generating correct transcripts with proper abundance. This study investigated the roles of histone H3 methylations and chromatin remodelling genes on the regulation of transcription initiation in yeast at a genome-scale, highlighting the impact of MINC depletion on stimulating new transcription initiation sites and the contribution of histone methylation to repressing transcription initiation in coding regions.
Article
Biochemistry & Molecular Biology
Thomas Gremminger, Zhenwei Song, Juan Ji, Avery Foster, Kexin Weng, Xiao Heng
Summary: The additional intermolecular interaction between tRNA(Lys3) and vRNA in HIV-1 is a conserved mechanism that protects vRNA from RNaseH degradation and promotes RT activity in mature virions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yumei Li, Yanwen Zhu, Shu Feng, Yuji Ishida, Tsu-Pei Chiu, Takeshi Saito, Sean Wang, David K. Ann, Jing-hsiung James Ou
Summary: Macrophages display plasticity in response to hepatitis B virus (HBV) infection, producing IL-10 to suppress viral replication. However, the virus can metabolically reprogram macrophages to minimize the host antiviral response.
Article
Food Science & Technology
Emilie Larocque, Valerie Levesque, Dominic Lambert
Summary: This study adapted crystal digital RT-PCR (RT-cdPCR) assays for the detection and quantification of norovirus and hepatitis A virus in frozen raspberry samples. The results showed that RT-cdPCR is sensitive and precise, and can be used for quantitative measurements at low levels of contamination.
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
(2022)
Article
Infectious Diseases
Sayamon Hongjaisee, Natteewan Doungjinda, Woottichai Khamduang, Tanawan Samleerat Carraway, Jiraprapa Wipasa, Jose D. Debes, Khuanchai Supparatpinyo
Summary: The study developed a reverse transcription loop-mediated isothermal amplification (RTLAMP) assay for detecting hepatitis C virus (HCV) in a single closed tube. The assay showed high sensitivity, specificity, and stability in detecting different HCV genotypes, making it a potentially useful tool for identifying individuals in need of HCV treatment, particularly in resource-limited settings.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Virology
Nirmala Gupta, Minako Ogino, Dean E. Watkins, Tiffany Yu, Todd J. Green, Tomoaki Ogino
Summary: The phosphorylated protein is a critical co-factor in the transcription and replication of nonsegmented negative-strand RNA viruses. Through a series of deletion mutation experiments on the P protein of vesicular stomatitis virus, it was found that the region encompassing residues 51-104 is the transactivation domain of the P protein, which is essential for terminal de novo initiation of synthesis of leader RNA and anti-genome/genome.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Juergen Beck, Stefan Seitz, Chris Lauber, Michael Nassal
Summary: Hepadnaviruses and nackednaviruses, despite their significant differences in phylogeny and genome organization, both utilize a replication mechanism involving protein-priming and template synthesis from epsilon RNA element, suggesting the establishment of this replication mode in their ancient common ancestor. The discovery of conserved cis elements crucial for replication in both virus families at similar positions in their genomes indicates a widespread and evolutionarily robust principle of genome replication that dates back more than 400 million years ago.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Lauriane Lecoq, Shishan Wang, Marie Dujardin, Peter Zimmermann, Leonard Schuster, Marie-Laure Fogeron, Mathilde Briday, Maarten Schledorn, Thomas Wiegand, Laura Cole, Roland Montserret, Stephane Bressanelli, Beat H. Meier, Michael Nassal, Anja Bockmann
Summary: A specific high-affinity pocket factor can trigger a conformational change in the capsid of hepatitis B virus, similar to a maturation signal. This interaction leads to the formulation of a synergistic double interaction hypothesis, providing a new concept for therapeutic interference with HBV envelopment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Zhongwei Chen, Yu Wang, XingYue Wang, Zicheng Xiao, Pingfan Wu, Kanghong Hu
Summary: Three original hexavanadate-based materials were synthesized and their structures were characterized by various analytical techniques. The compounds exhibited diverse packing manners due to different hydrogen-bonding interactions. PyBOP was found to be more effective than common EDCI/HOBt as a condensing agent. The study provides experimental guidance for the rational design of POM-based organic-inorganic hybrids.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Marie-Laure Fogeron, Lauriane Lecoq, Laura Cole, Roland Montserret, Guillaume David, Adeline Page, Frederic Delolme, Michael Nassal, Anja Boeckmann
Summary: This study established the phosphorylation sites in the human hepatitis B virus large envelope protein and suggested their potential functional role in viral life cycle. Further investigation on the mechanism of virion formation or cell entry is warranted.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Morgane Callon, Alexander A. Malar, Lauriane Lecoq, Marie Dujardin, Marie-Laure Fogeron, Shishan Wang, Maarten Schledorn, Thomas Bauer, Michael Nassal, Anja Bockmann, Beat H. Meier
Summary: This study reports a new solid-state NMR technique that allows for the detection and characterization of the C-terminal domain of the hepatitis B virus capsid protein. It extends the capabilities of solid-state NMR and can provide insights into other flexible protein domains.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Long-Sheng Wang, Chao Guo, Da Hu, Yan-Xi Zhao, Hui-Hui Liu, Yu-Jia Dong, Shang-Bin Sun, Xing Liu, Kang-Hong Hu, Yan-Hong Wei
Summary: A class of iodobenzoyldiazenido-functionalized POMs were synthesized and characterized. Some of these compounds demonstrated potent inhibitory activity against coxsackievirus B3.
FRONTIERS IN CHEMISTRY
(2022)
Editorial Material
Gastroenterology & Hepatology
Michael Nassal
Article
Multidisciplinary Sciences
Yang Wang, Wenjie Yuan, Siqi Guo, Qiqi Li, Xiaomei Chen, Cheng Li, Qianying Liu, Lei Sun, Zhenguo Chen, Zhenghong Yuan, Cheng Luo, Shijie Chen, Shuping Tong, Michael Nassal, Yu-Mei Wen, Yong-Xiang Wang
Summary: Researchers have discovered a 33-residue peptide that can improve the solubility and stability of multiple scFvs produced in Escherichia coli. This peptide tag, called P17, increases the solubility of scFvs up to 11.6 fold and enhances their thermostability. Additionally, scFvs with the P17 tag show higher antigen-binding affinity and virus-neutralizing activity. These findings have important implications for the research, production, and application of scFv.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Gastroenterology & Hepatology
Fabien Zoulim, Adam Zlotnick, Stephanie Buchholz, Eric Donaldson, John Fry, Anuj Gaggar, Jianming Hu, Michael Kann, Oliver Lenz, Kai Lin, Nagraj Mani, Michael Nassal, William Delaney, Su Wang, Gabriel Westman, Veronica Miller, Harry L. A. Janssen
Summary: This article proposes a naming convention for HBV core protein-targeting antiviral products to accelerate the development of drugs for Hepatitis B virus.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Oncology
Qinglin Ding, Hanluo Li, Zhigao Xu, Kanghong Hu, Qifa Ye
Summary: CFHR4 is an important gene associated with hepatocellular carcinoma (HCC), and its low expression level is significantly related to the prognosis of HCC and the level of immune infiltration. CFHR4 plays important roles in regulating the initiation and progression of HCC and could be a potential biomarker for the diagnosis and prognosis of HCC.
FRONTIERS IN ONCOLOGY
(2022)
Review
Virology
Kanghong Hu, Rominah Onintsoa Diarimalala, Chenguang Yao, Hanluo Li, Yanhong Wei
Summary: Enterovirus A71 (EV-A71) enters host cells through attachment, endocytosis, and uncoating stages. The main receptor hSCARB-2 and the secondary receptor PSGL-1 have been identified, along with other co-receptors. Understanding the complex interaction between the virus and host proteins and signaling pathways is critical in developing therapeutic approaches against EV-A71. Significant progress has been made in the development of inhibitors targeting receptors/co-receptors, virus capsids, signaling pathways, and other strategies.
Article
Multidisciplinary Sciences
Sara Pfister, Julius Rabl, Thomas Wiegand, Simone Mattei, Alexander A. Malaer, Lauriane Lecoq, Stefan Seitz, Ralf Bartenschlager, Anja Boeckmann, Michael Nassal, Daniel Boehringer, Beat H. Meier
Summary: The discovery of nackednaviruses provides new insight into the evolutionary history of hepatitis B virus (HBV). Both HBV and nackednaviruses share a common ancestor, but HBV acquired an envelope during evolution while nackednaviruses remained non-enveloped. The capsid structure of African cichlid nackednavirus (ACNDV) is very similar to HBV, with only minor structural differences.
NATURE COMMUNICATIONS
(2023)
Review
Nutrition & Dietetics
Kanghong Hu, Huizhong Huang, Hanluo Li, Yanhong Wei, Chenguang Yao
Summary: Diabetes mellitus is a complex disorder that requires lifelong dependence on glucose-lowering drugs. The advent of oral peptide drugs, such as semaglutide, brings hope to patients with chronic diabetes. This review summarizes the anti-diabetic activities and mechanisms of peptides from legumes and discusses the prospects of these peptide-based drugs in type 2 diabetes management.
Article
Pharmacology & Pharmacy
Yanhong Wei, Da Hu, Dong Li, Kanghong Hu, Qian Zhang, Huihui Liu, Qun He, Chenguang Yao, Hanluo Li, Jun Wang
Summary: A series of 2-Benzoxyl-Phenylpyridine derivatives were tested for their antiviral activities against EV71, and some of these compounds showed excellent effects on inhibiting EV71 replication. They could reduce cytopathic effects, decrease progeny viral yields, and exhibited similar or better antiviral activities compared to ribavirin. Compound WY7 was found to potently inhibit the 3C protease of EV71 and partially affect the activity of 3D polymerase. Molecular binding modeling suggested that WY7 could insert into the substrate-binding pocket of EV71 3C protease, blocking the recognition of substrates and inhibiting its activity.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Mathilde Briday, Francois Halle, Lauriane Lecoq, Sylvie Radix, Juliette Martin, Roland Montserret, Marie Dujardin, Marie-Laure Fogeron, Michael Nassal, Beat H. Meier, Thierry Lomberget, Anja Bockmann
Summary: Hepatitis B virus (HBV) is a significant human pathogen and its capsid-forming core protein (Cp) plays a key role in envelopment. Recent studies have found that Triton X-100, a detergent used in Cp purification, strongly binds to the hydrophobic pocket of Cp. The aromatic moiety is crucial for binding, while the aliphatic chain affects binding affinity. Moreover, the hydrophilic tail shows high tolerance to changes in length and type.