Article
Virology
Susannah Stephenson-Tsoris, John L. Casey
Summary: This study identified the start site for HDV genome RNA synthesis as position 1646 and revealed some differences in the synthesis process. The findings are important for targeting virus replication.
JOURNAL OF VIROLOGY
(2022)
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)
Article
Gastroenterology & Hepatology
Frauke Lange, Jonathan Garn, Holda A. Anagho, Florian W. R. Vondran, Thomas von Hahn, Thomas Pietschmann, Arnaud Carpentier
Summary: hPSC-derived HLCs become susceptible to HDV after acquiring the viral receptor NTCP. Infection leads to an innate immune response and upregulation of interferon-stimulated genes. Pre-treatment with IFN α2b reduces viral infection, while Myrcludex efficiently blocks infection and prevents immune activation.
LIVER INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Jiqin Wu, Xinyu Wang, Qiaojie Liu, Guoliang Lu, Peng Gong
Summary: This study presents crystal structures of the RNA-dependent RNA polymerase complex from dengue virus serotype 2, revealing a dramatic refolding of the priming element during elongation and confirming its essential interactions with the RNA duplex backbone for enzyme stability. Enzymology data further suggest that the critical refolding transition of the priming element likely occurs after the synthesis of a 4- to 5-nucleotide product.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Chao -Wei Hsu, Hsueh-Ying Hsu, Chien -Hung Chen, Mei Chao
Summary: RNA editing is crucial for generating the large delta antigen in hepatitis delta virus (HDV). The unbranched rod-like RNA structures surrounding the editing site play a crucial role in regulating the editing rates of different HDV genotypes. The size of the bulge upstream of the editing site and the base-pairing length downstream also influence the editing rate of HDV-4.
Review
Virology
Kavitha Ramaswamy, Mariya Rashid, Selvarajan Ramasamy, Tamilselvan Jayavelu, Sangita Venkataraman
Summary: This review explores the structural differences of RdRPs in RNA binding and polymerization mechanisms, based on recent studies of RdRP complexes with various cofactors, RNA moieties, analogs, and inhibitors.
Article
Microbiology
Afzaal M. Shareef, Barbara Ludeke, Paul Jordan, Jerome Deval, Rachel Fearns
Summary: The study explores the RNA synthesis initiation properties of polymerases from three different non-segmented negative strand RNA virus families, revealing that they are fundamentally similar in their initiation properties but differ in their ability to engage in back-priming activity. This suggests potential structural differences between polymerases from different virus families and highlights the importance of understanding the similarities and differences in developing antiviral drugs with broad efficacy.
Review
Microbiology
Jun Zi, Xiuzhu Gao, Juan Du, Hongqin Xu, Junqi Niu, Xiumei Chi
Summary: Hepatitis Delta Virus (HDV) is the smallest mammalian single-stranded RNA virus that requires host cells and hepatitis B virus (HBV) for its unique life cycle. This review details the specific regions on HDV antigens that drive HDV to utilize host cell machinery for viral replication and entry, and highlights new therapies with better efficacy and fewer adverse reactions, such as Bulevirtide, Lonafarnib, and Nucleic acid polymers.
FRONTIERS IN MICROBIOLOGY
(2022)
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)
Article
Gastroenterology & Hepatology
Ohad Etzion, Saeed Hamid, Yoav Lurie, Edward J. Gane, David Yardeni, Sarah Duehren, Nimrah Bader, Anat Nevo-Shor, Saleh Muhammad Channa, Scott J. Cotler, Minaz Mawani, Om Parkash, Harel Dahari, Ingrid Choong, Jeffrey S. Glenn
Summary: This study investigates a new treatment for chronic HDV infection using Lambda monotherapy, which shows virologic response during and following treatment.
Article
Biochemistry & Molecular Biology
Peng Gong
Summary: This study focuses on viral RdRP NAC and related mechanisms that have not been structurally clarified, discussing potential factors such as movement along the template strand, cleavage of the product strand, and the impact of non-cognate NTP substrates on the NAC process, emphasizing the complications and challenges that may arise in these areas.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
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
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
Chemistry, Multidisciplinary
Wenjing Wang, Wenkang Li, Zhiyuan Wen, Chong Wang, Weilong Liu, Yufang Zhang, Juncheng Liu, Tianze Ding, Lei Shuai, Gongxun Zhong, Zhigao Bu, Lingbo Qu, Maozhi Ren, Fuguang Li
Summary: Gossypol (GOS), identified from natural products, has been found to block SARS-CoV-2 RdRp and inhibit viral replication. It also exhibits broad-spectrum antiviral activity against different types of coronaviruses. These findings suggest that GOS could be a promising candidate for combating COVID-19 and other coronavirus outbreaks.
Article
Virology
Heli A. M. Monttinen, Janne J. Ravantti, Minna M. Poranen
Summary: RNA viruses evolve rapidly, making traditional sequence-based phylogenetic methods less effective in reconstructing relationships among them. Protein structures evolve more slowly and can show similarity even when sequences do not. The structure-based phylogenetic tree of viral RdRps reflects their functional differentiation.