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
Immunology
Maura Dandri, Antonio Bertoletti, Marc Luetgehetmann
Summary: Chronic infections with human hepatitis viruses, particularly hepatitis B virus (HBV) and hepatitis D virus (HDV), have a significant impact on human health globally. Understanding how these viruses interact with hepatocytes' innate immune responses is crucial for developing effective therapeutic strategies. Infected hepatocytes by these viruses influence immune system functions and affect the progression of liver diseases.
SEMINARS IN IMMUNOPATHOLOGY
(2021)
Review
Immunology
Fenglin Zhao, Xiaoyu Xie, Xu Tan, Hongli Yu, Miaomiao Tian, Huanran Lv, Chengyong Qin, Jianni Qi, Qiang Zhu
Summary: Approximately 250 million people worldwide suffer from chronic Hepatitis B virus infection, leading to significant public health challenges. Despite available vaccines and antiviral drugs, curing chronic hepatitis B remains a distant goal. HBV-encoded proteins, including surface antigen, core antigen, envelope antigen, HBx, and polymerase, play crucial roles in viral persistence and liver pathogenesis, offering potential avenues for new CHB therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Tarik Asselah, Mario Rizzetto
Summary: Hepatitis D virus (HDV), also known as hepatitis delta virus, is a defective, hepatotropic pathogenic agent. It requires the hepatitis B surface antigen (HBsAg) provided by hepatitis B virus (HBV) for its life cycle. HDV is mainly transmitted through contaminated syringes used by intravenous drug users. It is characterized by unique biological characteristics and severe medical effects. The global prevalence of HDV infection remains uncertain, and effective therapies are urgently needed.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Gastroenterology & Hepatology
Zhenfeng Zhang, Stephan Urban
Summary: Chronic hepatitis D (CHD) is the most severe form of viral hepatitis caused by the smallest known human virus, HDV, which replicates in the nucleus of hepatocytes. The IFN response strongly suppresses the cell division-mediated spread of HDV genomes, but has minimal effect on HDV RNA replication in already infected, resting hepatocytes. Recent research has uncovered key determinants of HDV persistence and new antivirals that interfere with the replication cycle, showing promising therapeutic perspectives.
JOURNAL OF HEPATOLOGY
(2021)
Editorial Material
Virology
Syeda Kanza Kazmi, Fatima Muhammad Asad Khan, Valentino Natoli, Reem Hunain, Zarmina Islam, Ana Carla dos Santos Costa, Shoaib Ahmad, Mohammad Yasir Essar
Summary: Hepatitis is a significant cause of mortality worldwide, with around 1.34 million deaths annually. Africa is not immune to this issue, with an estimated 100 million individuals infected with Hepatitis B or C. The continent, already fragile, is further burdened by the onset of the COVID-19 pandemic, which could potentially worsen the threat from viral diseases like Hepatitis. Strengthening prevention policies is essential for Africa to build resilience against such threats.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Gastroenterology & Hepatology
Maria B. Pisano, Cecilia G. Giadans, Diego M. Flichman, Viviana E. Re, Maria Preciado, Pamela Valva
Summary: Viral hepatitis caused by different viruses remains a significant public health issue with many unresolved problems, including pathogenesis, treatment, and vaccine development. This review focuses on key issues such as epidemiology, diagnostic methodology, and therapy of viral hepatitis.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Wenshi Wang, Florian A. Lempp, Franziska Schlund, Lisa Walter, Charlotte C. Decker, Zhenfeng Zhang, Yi Ni, Stephan Urban
Summary: Research has shown that HDVs from different genotypes replicate with varying efficacies. Variations in HDV genomes and HBV envelope proteins are major determinants of HDV egress and entry efficacy.
JOURNAL OF HEPATOLOGY
(2021)
Review
Immunology
Shuling Wu, Wei Yi, Yuanjiao Gao, Wen Deng, Xiaoyue Bi, Yanjie Lin, Liu Yang, Yao Lu, Ruyu Liu, Min Chang, Ge Shen, Leiping Hu, Lu Zhang, Minghui Li, Yao Xie
Summary: Functional cure is considered achieved when chronic hepatitis B patients achieve HBsAg seroclearance after treatment. Clearing the virus is challenging due to the difficulty in clearing both cccDNA and integrated dslDNA. High levels of HBsAg in the serum lead to immune system failure, making it unable to produce an effective antiviral response. Only less than 1% of chronic hepatitis B patients are cured annually with antiviral treatment. Coinfection with other viruses such as HIV, HCV, and HDV makes it even more difficult to cure. However, it has been found that patients with coinfection have a higher probability of achieving HBsAg seroclearance, especially those with HBV/HIV coinfection with up to 36% 5-year seroclerance rate. This interesting phenomenon is related to the functional reconstruction of the immune system after antiretroviral therapy (ART).
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Zhijiang Miao, Zhenrong Xie, Li Ren, Qiuwei Pan
Summary: HDV infection can cause severe hepatitis leading to cirrhosis and hepatocellular carcinoma, requiring advanced scientific knowledge and joint efforts from multi-stakeholders to combat effectively.
CHINESE MEDICAL JOURNAL
(2022)
Article
Microbiology
Iman Waheed Khan, Mati Ullah Dad Ullah, Mina Choudhry, Mukarram Jamat Ali, Muhammad Ashar Ali, Sam L. K. Lam, Pir Ahmad Shah, Satinder Pal Kaur, Daryl T. Y. Lau
Summary: HBV infection is a global public health issue and a major cause of cirrhosis and HCC; current therapies for chronic hepatitis B and D are suboptimal and new therapeutic agents targeting different stages of viral replicative cycle are necessary; promising compounds such as entry inhibitors, cccDNA inhibitors, siRNAs, capsid assembly modulators and nucleic acid polymers are in various stages of clinical development.
Article
Biology
Haifeng C. Xu, Ruifeng Wang, Prashant V. Shinde, Lara Walotka, Anfei Huang, Gereon Poschmann, Jun Huang, Wei Liu, Kai Stuehler, Heiner Schaal, Andreas Bergthaler, Aleksandra A. Pandyra, Cornelia Hardt, Karl S. Lang, Philipp A. Lang
Summary: Using different strains of the lymphocytic choriomeningitis virus (LCMV), Xu, Wang et al. demonstrate that slower viral propagation limits type I interferon (IFN-I) production and viral persistence in mice. This study suggests reduced viral propagation as a mechanism for immune evasion and viral persistence.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Takeshi Chida, Yuji Ishida, Sho Morioka, Go Sugahara, Christine Han, Bill Lam, Chihiro Yamasaki, Remi Sugahara, Meng Li, Yasuhito Tanaka, T. Jake Liang, Chise Tateno, Takeshi Saito
Summary: Hepatitis delta virus (HDV), a satellite virus of HBV, induces a potent and persistent activation of the IFN system in human hepatocytes, while HBV is not capable of triggering a hepatic antiviral response. HDV's constitutive activation of the hepatic IFN system suppresses HBV but modestly inhibits HDV, creating a paradoxical mode of viral interference. Furthermore, the study reveals that HDV-induced constitutive IFN system activation leads to IFN refractoriness, rendering therapeutic IFNs ineffective.
Review
Gastroenterology & Hepatology
Norah A. Terrault, Miriam T. Levy, Ka Wang Cheung, Gonzague Jourdain
Summary: The management of viral hepatitis in pregnancy requires special consideration due to the unique characteristics of each hepatitis virus and their impact on maternal and infant outcomes. Preventing mother-to-child transmission is crucial in reducing the global burden of chronic viral hepatitis.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Rheza Gandi Bawono, Takayuki Abe, Mengting Qu, Daisuke Kuroki, Lin Deng, Chieko Matsui, Akihide Ryo, Tetsuro Suzuki, Yoshiharu Matsuura, Masaya Sugiyama, Masashi Mizokami, Kunitada Shimotohno, Ikuo Shoji
Summary: The study demonstrates that the ISGylation modification of HBx protein by ISG15 plays a pro-viral role in HBV replication and is involved in resistance to IFN-α. HERC5 is identified as an E3 ligase for HBx-ISGylation, and USP18 is involved in regulating HBV replication in response to ISG15.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Cell Biology
M. Cyrus Maher, Istvan Bartha, Steven Weaver, Julia di Iulio, Elena Ferri, Leah Soriaga, Florian A. Lempp, Brian L. Hie, Bryan Bryson, Bonnie Berger, David L. Robertson, Gyorgy Snell, Davide Corti, Herbert W. Virgin, Sergei L. Kosakovsky Pond, Amalio Telenti
Summary: This study predicts future variants of SARS-CoV-2 by analyzing various factors affecting its evolution, including ACE2-mediated transmissibility and host immunity. The researchers successfully identified mutations that will emerge in different phases of the pandemic and assessed their impact on therapeutic antibodies. This modeling approach has important implications for predicting emerging variants of SARS-CoV-2 and can be applied to other rapidly evolving pathogens.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Microbiology
Christian Heuss, Paul Rothhaar, Rani Burm, Ji-Young Lee, Philipp Ralfs, Uta Haselmann, Luisa J. Stroh, Ombretta Colasanti, Cong Si Tran, Noemi Schafer, Paul Schnitzler, Uta Merle, Ralf Bartenschlager, Arvind H. Patel, Frederik Graw, Thomas Krey, Vibor Laketa, Philip Meuleman, Volker Lohmann
Summary: This study reports an efficient infectious cell culture model for hepatitis C virus (HCV), which can be used for studying infection mechanisms and developing vaccines. The model, generated from a consensus gt1b genome, underwent long-term passaging to adapt and produce high levels of transmissible infectivity. The study's findings are important for understanding the transmission mechanisms of HCV and for research and prevention of HCV.
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)
Review
Biochemistry & Molecular Biology
Amelie Vogt, Sabrina Wohlfart, Stephan Urban, Walter Mier
Summary: The article discusses the issue of coinfection with hepatitis B and D viruses and the latest developments in treatment, emphasizing the importance of understanding the viral lifecycle in the development of new therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
Gastroenterology & Hepatology
Florian A. Lempp, Tassilo Volz, Elisabetta Cameroni, Fabio Benigni, Jiayi Zhou, Laura E. Rosen, Julia Noack, Fabrizia Zatta, Hannah Kaiser, Siro Bianchi, Gloria Lombardo, Stefano Jaconi, Lucia Vincenzetti, Hasan Imam, Leah B. Soriaga, Nadia Passini, David M. Belnap, Andreas Schulze, Marc Luetgehetmann, Amalio Telenti, Andrea L. Cathcart, Gyorgy Snell, Lisa A. Purcell, Christy M. Hebner, Stephan Urban, Maura Dandri, Davide Corti, Michael A. Schmid
Summary: This study describes a monoclonal antibody that targets the surface antigen of hepatitis B virus (HBV) and shows potential for treating chronic hepatitis B and chronic hepatitis D. The antibody effectively neutralizes HBV and HDV infections in vitro and reduces viral levels in human liver-chimeric mice.
JOURNAL OF HEPATOLOGY
(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.
Article
Gastroenterology & Hepatology
Bingqian Qu, Firat Nebioglu, Mila M. Leuthold, Yi Ni, Pascal Mutz, Juergen Beneke, Holger Erfle, Florian W. R. Vondran, Ralf Bartenschlager, Stephan Urban
Summary: Neddylation pathway plays a crucial role in HBV infection and integration of viral DNA, and blocking this pathway may offer an attractive approach for the functional cure of chronic hepatitis B.