Article
Gastroenterology & Hepatology
Maika S. Deffieu, Camille M. H. Clement, Cristina M. Dorobantu, Emma Partiot, Yonis Bare, Orestis Faklaris, Benjamin Riviere, Nilda Vanesa Ayala-Nunez, Thomas F. Baumert, Philippe Ronde, Yves Mely, Vincent Lucansky, Raphael Gaudin
Summary: This study provides robust evidence that HCV particles interact with OCLN away from TJs and sheds mechanistic insights regarding the manipulation of transmembrane receptor localization by extracellular virus particles.
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
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
Laura Corneillie, Irma Lemmens, Claire Montpellier, Martin Ferrie, Karin Weening, Freya Van Houtte, Xavier Hanoulle, Laurence Cocquerel, Ali Amara, Jan Tavernier, Philip Meuleman
Summary: This study revealed the specific mechanism of cellular entry of the hepatitis E virus (HEV), showing that phosphatidylserine (PS) on the viral membrane and TIM1 protein play crucial roles in the envelope form of the virus.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Virology
Yongqi Li, Yang Yang, Tianyang Li, Zhengmin Wang, Chunfeng Gao, Rilin Deng, Faxiang Ma, Xinyang Li, Licong Ma, Renyun Tian, Huiyi Li, Haizhen Zhu, Lei Zeng, Yanhang Gao, Guoyue Lv, Junqi Niu, Ian Nicholas Crispe, Zhengkun Tu
Summary: HBV infection activates host immune response, leading to the production of antiviral immunity and also triggers anti-HCV immunity, which suppresses the replication of both viruses.
JOURNAL OF VIROLOGY
(2023)
Review
Microbiology
Emmanuelle V. LeBlanc, Youjin Kim, Chantelle J. Capicciotti, Che C. Colpitts
Summary: This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.
Article
Biochemistry & Molecular Biology
Hyung Chul Ryu, Marc Windisch, Jee Woong Lim, Inhee Choi, Eun Kyu Lee, Hye Hyun Yoo, Tae Kon Kim
Summary: Novel small-molecule inhibitors of hepatitis C virus (HCV) were synthesized and screened, with J2H-1701 identified as the optimized lead compound for HCV entry inhibition based on its potent antiviral activity and safety profile. This compound showed effective multi-genotypic antiviral activity and potential interaction with the HCV E2 glycoprotein, suggesting it as a candidate drug for HCV entry inhibition.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Jisu Hong, Youngjin Choi, Yoonjoo Choi, Jiwoo Lee, Hyo Jeong Hong
Summary: By conducting experiments and structural analysis, it was found that 1A8 can effectively block HBV infection of different genotypes, making it a promising candidate for the prevention and treatment of HBV infection.
Review
Gastroenterology & Hepatology
Hui-Chun Li, Chee-Hing Yang, Shih-Yen Lo
Summary: HCV, an obligatory intracellular pathogen, relies heavily on host cells for successful propagation. Its lifecycle includes stages such as viral entry, protein translation, RNA replication, viral assembly, and release, with hundreds of cellular factors identified over three decades of research. These factors, some of which are targeted for anti-HCV therapies, provide valuable insight into HCV replication strategies.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Pharmacology & Pharmacy
Jiaxuan Chen, Jia Hou, Rong Na, Bin Zhou, Jinlin Hou, De-Ke Jiang
Summary: This study found that overexpression of BST2 can improve the anti-HBV effect of IFN-α treatment, and BST2_rs9576 is an effective indicator for predicting the therapy response of PegIFN alpha-treated patients with CHB. The PGS model has the potential to enhance the ability of PegIFN alpha therapy response.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Virology
Yudi Pan, Longjun Guo, Qian Miao, Ling Wu, Zhaoyang Jing, Jin Tian, Li Feng
Summary: This study identifies THBS3 as a critical player in PRV binding and subsequent membrane fusion and entry, providing insights into the initial events of alpha herpesvirus infections.
JOURNAL OF VIROLOGY
(2023)
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
Biochemical Research Methods
Mariia Antipchik, Evgenia Korzhikova-Vlakh, Dmitry Polyakov, Irina Tarasenko, Jekaterina Reut, Andres Opik, Vitali Syritski
Summary: This study aimed to develop a biosensor for direct detection of HCV surface antigen E2, using a recombinant LEL fragment and synthetic peptides as molecular recognition elements. The linear peptide was selected for its cost-effectiveness and ease of preparation, demonstrating selectivity towards E2 in the presence of interfering proteins, and effective detection of E2 bound to HC VMPs in different solutions.
ANALYTICAL BIOCHEMISTRY
(2021)
Review
Gastroenterology & Hepatology
Alessandra Mangia, Rosa Cotugno, Giovanna Cocomazzi, Maria Maddalena Squillante, Valeria Piazzolla
Summary: The World Health Organization's goal of eliminating Hepatitis C virus (HCV) by 2030 using direct-acting antiviral treatments has become less attainable post the 2020 pandemic of coronavirus disease 2019. Therefore, a more realistic approach of micro-elimination in population segments where targeted strategies of prevention and treatment are easily attained has been promoted in Europe. Active involvement of stakeholders and community participation are essential components for the success of a micro-elimination project tailored at the geographical level according to HCV epidemiology and individual country's income.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
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
Gastroenterology & Hepatology
Valentin Sencio, Arnaud Machelart, Cyril Robil, Nicolas Benech, Eik Hoffmann, Chloe Galbert, Lucie Deryuter, Severine Heumel, Aline Hantute-Ghesquier, Anne Flourens, Priscille Brodin, Fabrice Infanti, Virgile Richard, Jean Dubuisson, Corinne Grangette, Thierry Sulpice, Isabelle Wolowczuk, Florence Pinet, Vincent Prevot, Sandrine Belouzard, Francois Briand, Martine Duterque-Coquillaud, Harry Sokol, Francois Trottein
Summary: Mounting evidence suggests that the gut plays a critical role during respiratory viral infections. Using a hamster model, this study found that SARS-CoV-2 infection led to intestinal inflammation, altered intestinal barrier property, liver inflammation, and disrupted lipid metabolism. The changes were accompanied by alterations in the gut microbiota composition, characterized by an increase in harmful bacterial taxa and a decrease in bacteria that produce SCFAs. These alterations in the gut microbiota were correlated with disease severity in hamsters.
Article
Microbiology
Sandrine Belouzard, Arnaud Machelart, Valentin Sencio, Thibaut Vausselin, Eik Hoffmann, Nathalie Deboosere, Yves Rouille, Lowiese Desmarets, Karin Seron, Adeline Danneels, Cyril Robil, Loic Belloy, Camille Moreau, Catherine Piveteau, Alexandre Biela, Alexandre Vandeputte, Severine Heumel, Lucie Deruyter, Julie Dumont, Florence Leroux, Ilka Engelmann, Enagnon Kazali Alidjinou, Didier Hober, Priscille Brodin, Terence Beghyn, Francois Trottein, Benoit Deprez, Jean Dubuisson
Summary: In this study, the researchers screened a library of drug compounds to identify potential antivirals against SARS-CoV-2. They discovered that clofoctol, an antibacterial drug used for respiratory tract infections, exhibited significant antiviral activity and had favorable safety and pharmacokinetic properties. In vivo experiments showed that clofoctol reduced inflammatory gene expression and pulmonary pathology. These findings suggest that clofoctol could be a promising therapeutic candidate for the treatment of COVID-19 patients.
Article
Chemistry, Multidisciplinary
Karina Nigoghossian, Basile Bouvet, Gautier Felix, Saad Sene, Luca Costa, Pierre-Emmanuel Milhet, Albano N. Carneiro Neto, Luis D. Carlos, Erwan Oliviero, Yannick Guari, Joulia Larionova
Summary: A new design of nano-objects containing a magnetic heater and a temperature emissive sensor has emerged as a promising tool in personalized nanomedicine. This system allows hyperthermia-assisted treatment under local temperature control and overcomes the challenge of controlling the morphology of nano-systems. The nanoparticles exhibit efficient heating capacity and possess a self-referencing temperature sensor with excellent thermal sensitivity.
Article
Chemistry, Multidisciplinary
Anthony Vial, Luca Costa, Patrice Dosset, Pietro Rosso, Gaelle Boutieres, Orestis Faklaris, Heiko Haschke, Pierre-Emmanuel Milhiet, Christine M. Doucet
Summary: Nuclear pore complexes (NPCs) are the gateways that control molecular transport between the nucleus and cytoplasm in eukaryotic cells. Recent studies have revealed the arrangement of most constituents in human NPCs using cryo-EM and AI-based protein modeling. However, the structure of the basket, which caps the nucleoplasmic side of the pore, remains poorly resolved. Using atomic force microscopy (AFM) and single molecule localization microscopy (SMLM), researchers discovered that the basket is highly flexible and can adopt different conformations, allowing diverse cargoes to pass through NPCs.
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.
Article
Chemistry, Medicinal
Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, Lowiese Desmarets, Yves Rouille, Julie Dumont, Adrien Herledan, Sandrine Warenghem, Catherine Piveteau, Paul Carr, Sarah Ikherbane, Francois-Xavier Cantrelle, Elian Dupre, Jean Dubuisson, Sandrine Belouzard, Florence Leroux, Benoit Deprez, Julie Charton
Summary: Since the end of 2019, the global outbreak of the coronavirus SARS-CoV-2 has caused a significant increase in infections and deaths worldwide. Researchers have identified two proteases, 3CLpro and papain-like protease, encoded by the virus that play a crucial role in the virus lifecycle. Targeting the 3CLpro, which is highly conserved within this viral family, a screening of over 89,000 small molecules led to the discovery of a potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, interaction with the protease, specificity against host proteases, and promising antiviral properties in cells are reported.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Biochemistry & Molecular Biology
Laura Corneillie, Irma Lemmens, Claire Montpellier, Martin Ferrie, Karin Weening, Freya Van Houtte, Xavier Hanoulle, Laurence Cocquerel, Ali Amara, Jan Tavernier, Philip Meuleman
Summary: This study revealed the specific mechanism of cellular entry of the hepatitis E virus (HEV), showing that phosphatidylserine (PS) on the viral membrane and TIM1 protein play crucial roles in the envelope form of the virus.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Stephanie Hutin, Janet R. Kumita, Vivien I. Strotmann, Anika Dolata, Wai Li Ling, Nessim Louafi, Anton Popov, Pierre- Emmanuel Milhiet, Martin Blackledge, Max H. Nanao, Philip A. Wigge, Yvonne Stahl, Luca Costa, Mark D. Tully, Chloe Zubieta
Summary: Liquid-liquid phase separation is a crucial mechanism for the dynamic compartmentalization of macromolecules in response to physicochemical factors. In the model plant Arabidopsis thaliana, the protein ELF3 drives temperature-sensitive growth by undergoing liquid-liquid phase separation. Through a combination of biochemical, biophysical, and structural techniques, this study investigates the behavior of the ELF3 protein with varying lengths of its poly-glutamine tract. The results show that the dilute phase of ELF3 forms a monodisperse higher-order oligomer, which undergoes pH- and temperature-sensitive phase separation, leading to the formation of a hydrogel.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Esther Martin de Fourchambault, Nathalie Callens, Jean-Michel Saliou, Marie Fourcot, Oceane Delos, Nicolas Barois, Quentin Thorel, Santseharay Ramirez, Jens Bukh, Laurence Cocquerel, Justine Bertrand-Michel, Guillemette Marot, Yasmine Sebti, Jean Dubuisson, Yves Rouille
Summary: Despite effective treatments for hepatitis C in clinics, issues remain regarding the liver disease induced by chronic hepatitis C virus (HCV) infection. This study identified alterations in peroxisome function and morphology in HCV-infected cells, particularly involving lipid metabolism and redox balance.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Cell Biology
Ye Fan, Cedric Pionneau, Federico Cocozza, Pierre-Yves Boelle, Solenne Chardonnet, Stephanie Charrin, Clotilde Thery, Pascale Zimmermann, Eric Rubinstein
Summary: This study reveals that CD9, CD81, and CD63, commonly used as protein markers for extracellular vesicles (EVs), have little impact on the protein composition of EVs released by MCF7 breast cancer cells. Knocking out CD9 and CD81 only significantly decreases the levels of CD9P-1 and EWI-2 in EVs. This suggests a marginal role of CD9, CD81, and CD63 in determining the protein composition of EVs and highlights the regulation of CD9P-1 and EWI-2 expression level and/or trafficking by CD9 and CD81.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Biochemistry & Molecular Biology
Lowiese Desmarets, Adeline Danneels, Julien Burlaud-Gaillard, Emmanuelle Blanchard, Jean Dubuisson, Sandrine Belouzard
Summary: The membrane protein of Middle East respiratory syndrome coronavirus (MERS-CoV) plays a crucial role in the virus assembly process. Proper intracellular trafficking and subcellular localization of the M protein are essential for virus formation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)