Article
Pharmacology & Pharmacy
Finny S. Varghese, Febrina Meutiawati, Mona Teppor, Sofie Jacobs, Carolien de Keyzer, Ezgi Taskopru, Esther van Woudenbergh, Gijs J. Overheul, Ellen Bouma, Jolanda M. Smit, Leen Delang, Andres Merits, Ronald P. van Rij
Summary: Drug repurposing is a promising strategy for identifying therapeutic interventions against novel and re-emerging viruses. This study found that posaconazole inhibits replication of multiple alphaviruses, broadening the spectrum of viruses that can be targeted by this drug.
ANTIVIRAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Mayuko Yagi, Minami Hama, Sayaka Ichii, Yurie Nakashima, Daiki Kanbayashi, Takako Kurata, Kosuke Yusa, Jun Komano
Summary: This study used CRISPR-Cas9 system to conduct a loss-of-function screening in human placenta-derived JAR cells, and identified sphingomyelin synthase 1 as a susceptibility factor for rubella virus infection. The study revealed the unique regulation of rubella virus replication by a host factor during the early and late phases of the viral life cycle.
Article
Biophysics
Ru Cheng, Fu Zhu, Min Huang, Qiang Zhang, Hui Hong Yan, Xiao Hui Zhao, Fu Kang Luo, Chun Mei Li, Hui Liu, Gao Lin Liang, Cheng Zhi Huang, Jian Wang
Summary: In this study, a new biosensor named hepatitis virus indicator was developed for the simultaneous detection of HBV and HCV. The biosensor utilized Exo III assisted signal amplification strategy and particle counting technology with a dark-field microscopy, enabling sensitive and selective detection.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biochemistry & Molecular Biology
Keiji Ueda, Yadarat Suwanmanee
Summary: The precise mechanism of HBV entry into cells is still largely unknown. However, researchers have identified ATP5B as an essential factor for HBV entry, which is believed to bind with myristoylated preS1 2-47. Knockdown of ATP5B in NTCP-expressing HepG2 cells reduced HBV infectivity, indicating that ATP5B is involved in the HBV entry process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Lenka Stejskal, Mphatso D. Kalemera, Charlotte B. Lewis, Machaela Palor, Lucas Walker, Tina Daviter, William D. Lees, David S. Moss, Myrto Kremyda-Vlachou, Zisis Kozlakidis, Giulia Gallo, Dalan Bailey, William Rosenberg, Christopher J. R. Illingworth, Adrian J. Shepherd, Joe Grove
Summary: This study reveals that the hypervariable region-1 (HVR-1) of the fusion proteins E1E2 in Hepatitis C Virus (HCV) has an autoinhibitory function that controls the activity of the proteins. The mechanism is turned off by host receptor interactions, allowing virus entry. Mutations or deletion of HVR-1 results in enhanced virus entry but increased sensitivity to neutralising antibodies.
Article
Chemistry, Multidisciplinary
Nicholas E. Brunk, Reidun Twarock
Summary: The genetic material of a virus is encapsulated in viral protein containers, which can be repurposed as virus-like particles in various nanotechnology applications, balancing stability for protection and instability for efficient release. The geometric characteristics of viral capsids, such as subunit layout and intersubunit interaction network, play a key role in disassembly behavior, with specific viral geometries favored in nature and offering guidance for virus-like particle design in nanotechnology.
Article
Medicine, General & Internal
Heiner Wedemeyer, Soo Aleman, Maurizia Rossana Brunetto, Antje Blank, Pietro Andreone, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Natalia Geyvandova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Annemarie Berger, Dmitry Manuilov, Vithika Suri, Qi An, Ben Da, John Flaherty, Anu Osinusi, Yang Liu, Uta Merle, Julian Schulzezur Wiesch, Stefan Zeuzem, Sandra Ciesek, Markus Cornberg, Pietro Lampertico
Summary: In this study, it was found that bulevirtide is effective in inhibiting the entry of hepatitis D virus and reducing the progression of liver disease in patients with chronic hepatitis B. The recommended dosage of bulevirtide is 2 mg or 10 mg per day.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Medicine, General & Internal
Heiner Wedemeyer, Soo Aleman, Maurizia Rossana Brunetto, Antje Blank, Pietro Andreone, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Natalia Geyvandova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Annemarie Berger, Dmitry Manuilov, Vithika Suri, Qi An, Ben Da, John Flaherty, Anu Osinusi, Yang Liu, Uta Merle, Julian Schulze zur Wiesch, Stefan Zeuzem, Sandra Ciesek, Markus Cornberg, Pietro Lampertico
Summary: Bulevirtide treatment reduces HDV RNA and ALT levels in patients with chronic hepatitis D, with a dose-dependent effect.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Microbiology
Christina Holmboe Olesen, Elias H. Augestad, Fulvia Troise, Jens Bukh, Jannick Prentoe
Summary: The study identifies critical E1/E2 substitutions for understanding HVR1-mediated NAb protection, emphasizing the need to overcome neutralizing antibody evasion mechanisms in developing effective HCV vaccine strategies.
Article
Virology
Erik M. Contreras, Gunner P. Johnston, David W. Buchholz, Victoria Ortega, I. Abrrey Monreal, J. Lizbeth R. Zamora, Tracy Cheung, Hector C. Aguilar
Summary: Cholesterol is involved in various stages of the viral life cycle for enveloped viruses. Nipah virus (NiV) is a highly pathogenic enveloped virus in the Henipavirus genus within the Paramyxoviridae family, and cholesterol levels influence both cell-cell membrane fusion during syncytium formation and virus-cell membrane fusion during viral entry. The levels of cholesterol impact early and late steps during the membrane fusion cascade in NiV, expanding our understanding of viral entry and cell-cell fusion processes.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Kamilla Toon, Mphatso D. Kalemera, Machaela Palor, Nicola J. Rose, Yasuhiro Takeuchi, Joe Grove, Giada Mattiuzzo
Summary: Due to increased and broadened screening efforts, the number of viral species in the Hepacivirus genus has rapidly expanded. Genetic features of hepaciviruses suggest they have adapted and evolved to hijack host proteins for efficient liver propagation. A study on GB virus B (GBV-B) found that claudin-1 is an essential entry factor, shared with hepatitis C virus (HCV), but with distinct mechanisms of entry. Understanding the molecular mechanisms of hepacivirus entry can inform the design of new vaccines and treatments targeting the first stage of HCV infection.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Toshikatsu Shibata, Hiroaki Okamoto, Mitsuhiko Moriyama, Tatsuo Kanda
Summary: In this study, several novel therapeutic drugs were investigated through a drug repositioning approach, with favipiravir identified as a potential antiviral against hepatitis A virus (HAV) infection. The study examined the replication of HAV and introduced nucleotide mutations in the HAV genome using different drugs. Favipiravir showed inhibitory effects on HAV replication and introduced more nucleotide mutations compared to ribavirin. Further in vivo experiments are needed to confirm the efficacy of favipiravir in treating severe HAV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Bingzhe Li, Han Wu, Ziping Miao, Linjie Hu, Lu Zhou, Yihan Lu
Summary: This study characterized the codon usage bias of different genotypes of Hepatitis E virus (HEV), revealing significant differences in codon usage between human, zoonotic, and animal HEV genotypes. The study also found that HEV is influenced by translation selection, leading to a unique dinucleotide usage pattern. Natural selection was identified as the main driver of codon usage bias in HEV, although mutation pressure also played a role in certain genotypes.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Virology
Julia Melchert, Helena Radbruch, Leif G. Hanitsch, Sally A. Baylis, Jorn Beheim-Schwarzbach, Tobias Bleicker, Jorg Hofmann, Terry C. Jones, Christian Drosten, Victor M. Corman
Summary: This study used high-throughput sequencing techniques, including targeted enrichment, to investigate the sequence diversity and intra-host diversity of HEV. Potential novel subtypes were identified in blood and ancient livestock samples, and ribavirin resistance mutations and HEV compartmentalization were found in a patient.
JOURNAL OF CLINICAL VIROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Karl Victor Gorzelnik, Junjie Zhang
Summary: Single-stranded RNA bacteriophages are small spherical RNA viruses that infect bacteria with retractile pili. Recent breakthroughs in high-resolution structural studies of two ssRNA phages, MS2 and Q beta, and their interaction with the host, E. coli, by cryo-electron microscopy provide insights into their infection cycle and potential therapeutic applications.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Review
Cell Biology
Vibhu Prasad, Ralf Bartenschlager
Summary: This review highlights the cellular trafficking factors, processes, and organelles relevant to the SARS-CoV-2 infection cycle and how viral proteins exploit and disrupt cellular transport.
BIOLOGY OF THE CELL
(2023)
Article
Gastroenterology & Hepatology
Natascha Roehlen, Marion Muller, Zeina Nehme, Emilie Crouchet, Frank Juhling, Fabio Del Zompo, Sara Cherradi, Francois H. T. Duong, Nuno Almeida, Antonio Saviano, Mirian Fernandez-Vaquero, Tobias Riedl, Houssein El Saghire, Sarah C. Durand, Clara Ponsolles, Marine A. Oudot, Romain Martin, Nicolas Brignon, Emanuele Felli, Patrick Pessaux, Antonin Lallement, Irwin Davidson, Simonetta Bandiera, Christine Thumann, Patrice Marchand, Solange Moll, Brandon Nicolay, Nabeel Bardeesy, Yujin Hoshida, Mathias Heikenwaelder, Roberto Iacone, Alberto Toso, Markus Meyer, Greg Elson, Tamas Schweighoffer, Geoffrey Teixeira, Mirjam B. Zeisel, Patrice Laquerriere, Joachim Lupberger, Catherine Schuster, Laurent Mailly, Thomas F. Baumert
Summary: In this study, the role of CLDN1 as a therapeutic target for hepatocellular carcinoma (HCC) was investigated using humanized monoclonal antibodies targeting non-junctional CLDN1 and various cell and animal models. The results demonstrated that targeting non-junctional CLDN1 significantly suppressed tumor growth and invasion, and affected tumor stemness, metabolism, oncogenic signaling, and the tumor immune microenvironment. These findings provide a rationale for targeting CLDN1 in the treatment of advanced HCC and lay the foundation for the development of CLDN1-specific monoclonal antibodies for clinical use.
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Nadine Gillich, Zhenfeng Zhang, Marco Binder, Stephan Urban, Ralf Bartenschlager
Summary: This study reveals that LGP2 is essential for the recognition of HDV through MDA5-mediated antiviral interferon (IFN) response. LGP2 induces IFN through RNA binding and ATPase activity, and stabilizes MDA5-RNA interaction for downstream signaling. The variant Q425R of LGP2 exhibits stronger inhibition on HDV infection and IFN response, and may contribute to a milder course of hepatitis D.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fanfan Zhao, Yongfen Xu, Na Liu, Dawei Lv, Yujie Chen, Zhi Liu, Xia Jin, Mingbing Xiao, Dimitri Lavillette, Jin Zhong, Ralf Bartenschlager, Gang Long
Summary: This study developed a rigorous method to study extracellular vesicles (EVs) from Zika virus (ZIKV)-infected cells. The EVs did not transmit infection, but displayed abundant E proteins which have an antigenic landscape similar to that of virions. These results suggest that modulation of E protein release via virions and EVs may present a new approach to regulating flavivirus-host interactions.
Article
Gastroenterology & Hepatology
Julie Lucifora, Dulce Alfaiate, Caroline Pons, Maud Michelet, Ricardo Ramirez, Floriane Fusil, Fouzia Amirache, Axel Rossi, Anne-Flore Legrand, Emilie Charles, Serena Vegna, Rayan Farhat, Michel Rivoire, Guillaume Passot, Nicolas Gadot, Barbara Testoni, Charlotte Bach, Thomas F. Baumert, Anastasia Hyrina, Rudolf K. Beran, Fabien Zoulim, Andre Boonstra, Hildegard Buening, Eloi R. Verrier, Francois-Loic Cosset, Simon P. Fletcher, Anna Salvetti, David Durantel
Summary: This study elucidates the molecular mechanisms underlying how HDV interferes with HBV in patients with chronic coinfection. The researchers found that HDV induces the expression of interferon-stimulated genes (ISGs), and these genes are upregulated in HDV/HBV-coinfected patients. Inhibiting the hepatocyte's response to interferon partially restores the levels of HBV.
JOURNAL OF HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Seng Gee Lim, Thomas F. Baumert, Carolina Boni, Ed Gane, Massimo Levrero, Anna S. Lok, Mala K. Maini, Norah A. Terrault, Fabien Zoulim
Summary: Functional cure of chronic hepatitis B (CHB), achieved through hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy, is the goal of current treatment. However, the rarity of achieving this cure with current therapy highlights the need for novel approaches. The three categories of treatment include reducing viral replication, reducing antigen load, and immunotherapies. Combination therapy of nucleos(t)ide analogues and immunotherapy shows promise in reducing HBsAg levels and inducing HBsAg loss in some patients, particularly those with low baseline HBsAg levels. Monitoring during therapy using viral and immunological biomarkers is important to predict HBsAg loss and understand its mechanisms.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Review
Cell Biology
Zeina Nehme, Natascha Roehlen, Punita Dhawan, Thomas F. F. Baumert
Summary: Tight junctions (TJs) are intercellular protein complexes that control paracellular permeability and cell polarity, and recent studies have shown their functional role beyond these classic functions. TJ proteins play crucial roles in cancer pathogenesis by modulating key signaling pathways that regulate cell proliferation, migration, and differentiation, as well as promoting stem cell phenotypes in cancer cells. Additionally, TJ proteins have been used as therapeutic targets and prognostic markers in preclinical and clinical studies. This review summarizes the functional role of TJ proteins in cancer biology and their potential for novel cancer prevention and treatment strategies.
Editorial Material
Gastroenterology & Hepatology
Nikolaus Jilg, Thomas F. Baumert
Article
Gastroenterology & Hepatology
Dieudonne Buh Kum, Hannah Vanrusselt, Abel Acosta Sanchez, Valerio Taverniti, Eloi R. Verrier, Thomas F. Baumert, Cheng Liu, Jerome Deval, Nikky Corthout, Sebastian Munck, Leonid Beigelman, Lawrence M. Blatt, Julian A. Symons, Pierre Raboisson, Andreas Jekle, Sandrine Vendeville, Yannick Debing
Summary: This study uncovers a novel mechanism of action for CAM-As in the treatment of chronic hepatitis B, where HBc aggregation induces cell death, leading to hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response.
Article
Multidisciplinary Sciences
Manon Venet, Margarida Sa Ribeiro, Elodie Decembre, Alicia Bellomo, Garima Joshi, Celia Nuovo, Marine Villard, David Cluet, Magali Perret, Remi Pescamona, Helena Paidassi, Thierry Walzer, Omran Allatif, Alexandre Belot, Sophie Trouillet-Assant, Emiliano P. Ricci, Marlene Dreux
Summary: The authors demonstrate that in severe SARS-CoV-2 infection, the function of plasmacytoid dendritic cells (pDC) is impaired, leading to reduced production of type I interferon and possibly lower viral control. This study suggests that pDC activation is essential to control SARS-CoV-2 infection, and failure to develop this response could be important in understanding severe cases of COVID-19.
NATURE COMMUNICATIONS
(2023)
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)
Article
Immunology
Huguette Simo Tchetgna, Francine S. Yousseu, Francois-Loic Cosset, Natalia Bezerra de Freitas, Basile Kamgang, Philip J. McCall, Roland Ndip Ndip, Vincent Legros, Charles S. Wondji
Summary: This study aimed to determine the prevalence of CCHFV in domestic ruminants and its vector ticks in Cameroon. CCHFV-specific antibodies were detected in the plasma samples of cattle, sheep, and goats, and ticks were screened for the presence of the virus. The seroprevalence of CCHFV was highest in cattle (98.18%) and one CCHFV strain was identified in ticks collected from cattle.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Virology
Claudius Speer, Maximilian Toellner, Louise Benning, Marie Bartenschlager, Heeyoung Kim, Christian Nusshag, Florian Kaelble, Marvin Reineke, Paula Reichel, Paul Schnitzler, Martin Zeier, Christian Morath, Wilhelm Schmitt, Raoul Bergner, Ralf Bartenschlager, Hanns-Martin Lorenz, Matthias Schaier
Summary: Emerging omicron subtypes with immune escape result in inadequate vaccine response in immunocompromised individuals like AAV patients. There is limited data on SARS-CoV-2 vaccination in AAV patients, and safety concerns exist regarding the use of mRNA vaccines in autoimmune diseases. This study provides insights into the neutralizing antibody response and reactogenicity of vaccines in AAV patients.
Article
Microbiology
Minh-Tu Pham, Ji-Young Lee, Christian Ritter, Roman Thielemann, Janis E. Meyer, Uta A. Haselmann, Charlotta E. Funaya, Vibor A. Laketa, Karl E. Rohr, Ralf A. Bartenschlager
Summary: Using imaging analyses, the study reveals that ApoE-LPs are stored in CD63-positive endosomes and released into circulation. The co-egress of ApoE-LPs and EVs along the late endosomal route and their transmission between cells are also observed. The hepatitis C virus hijacks this pathway to produce ApoE-associated EVs containing viral RNA. This research provides important insights into the role of ApoE in various diseases and the mechanism of cell-to-cell communication.
Article
Computer Science, Information Systems
Christian Ritter, Roman Thielemann, Ji-Young Lee, Minh Tu Pham, Ralf Bartenschlager, Karl Rohr
Summary: We introduce a software suite, consisting of ColocQuant and ColocJ, for colocalization analysis of spot-like objects in multi-channel fluorescence microscopy images. It provides efficient quantification and intuitive visualization of colocalization in two or three channels, as well as global statistics of particle properties. The software has been successfully applied to analyze live cell fluorescence microscopy image sequences of viral proteins in hepatitis C virus infected cells.