Article
Multidisciplinary Sciences
Yu Sun, Laura Abriola, Rachel O. Niederer, Savannah F. Pedersen, Mia M. Alfajaroe, Valter Silva Monteiro, Craig B. Wilen, Ya-Chi Ho, Wendy Gilbert, Yulia Surovtseva, Brett D. Lindenbach, Junjie U. Guo
Summary: The study found that merafloxacin can inhibit -1 PRF activity of SARS-CoV-2 and is similarly effective on other betacoronaviruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Virology
Sneha Munshi, Krishna Neupane, Sandaru M. Ileperuma, Matthew T. J. Halma, Jamie A. Kelly, Clarissa F. Halpern, Jonathan D. Dinman, Sarah Loerch, Michael T. Woodside
Summary: Recurrent outbreaks of novel zoonotic coronavirus diseases in recent years have emphasized the importance of developing therapeutics with broad-spectrum activity against coronaviruses. Researchers explored whether small-molecule inhibitors of -1 programmed ribosomal frameshifting in SARS-CoV-2 also inhibited this process in a range of bat coronaviruses. The results showed that some drugs had strong activity against a broad spectrum of coronaviruses, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics.
Article
Biochemistry & Molecular Biology
Xiaolan Huang, Zhihua Du
Summary: Pseudoknots play important roles in RNA viruses, such as stimulating ribosomal frameshifting or stop codon readthrough. Recent studies have confirmed the significance of three-stemmed pseudoknots in SARS-CoV-2 and related coronaviruses. Additional complex pseudoknots with various structural elements have also been identified, expanding our understanding of their regulatory functions in different virus families.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Editorial Material
Biology
Martina M. Yordanova, Pavel Baranov
Summary: The efficiency of ribosomes in shifting reading frames when decoding viral RNA may vary during an infection.
Review
Biochemistry & Molecular Biology
Kai-Chun Chang, Jin-Der Wen
Summary: -1 PRF is a translation mechanism used by viruses to regulate protein expression levels encoded on the same mRNA. It is rarely used by host human cells and is considered a potential target for antiviral drug development. -1 PRF occurs when ribosomes encounter specific mRNA signals impeding their translocation, leading to unique conformational changes essential for frameshifting.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Howard Gamper, Haixing Li, Isao Masuda, D. Miklos Robkis, Thomas Christian, Adam B. Conn, Gregor Blaha, E. James Petersson, Ruben L. Gonzalez, Ya-Ming Hou
Summary: The study investigates the translation of quadruplet codons by a +1-frameshifting tRNA SufB2, revealing that SufB2 initially uses triplet anticodon-codon pairing in the 0-frame to decode the quadruplet codon before shifting to the +1-frame during tRNA-mRNA translocation. The frameshifting mechanism of SufB2 involves perturbation of a crucial ribosome conformational change, highlighting the potential for engineering specific ribosome conformational changes to enhance genome recoding efficiency.
NATURE COMMUNICATIONS
(2021)
Review
Microbiology
Andrew S. S. Flies, Emily J. J. Flies, Nicholas M. M. Fountain-Jones, Ruth E. E. Musgrove, Rodrigo K. K. Hamede, Annie Philips, Matthew R. F. Perrott, Magdalena Dunowska
Summary: Wildlife is a significant source of emerging infectious diseases, including viruses from the order Nidovirales. This mini-review summarizes key findings on nidoviruses in vertebrate wildlife, focusing on two suborders: Arnidovirineae and Tornidovirineae. The available data on biology, disease associations, pathology, host population infections, and transmission routes are presented. Field-based studies and laboratory-based research are needed to understand virus-host-environment interactions, pathogenesis, and evolutionary histories of novel nidoviruses.
Review
Chemistry, Multidisciplinary
Viktoriya S. Anokhina, Benjamin L. Miller
Summary: Treating HIV-1 has moved from targeting viral enzymes to looking for new therapeutic targets, with -1 PRF gaining attention as a potential intervention point crucial for correct viral particle assembly. Despite being deleterious for the virus when dysregulated, -1 PRF is also exploited by other viruses like coronaviruses, including SARS-CoV-2, implying the importance of exploring similar strategies in antiviral development.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ekaterina Knizhnik, Stepan Chumakov, Julia Svetlova, Iulia Pavlova, Yuri Khodarovich, Vladimir Brylev, Vjacheslav Severov, Rugiya Alieva, Liubov Kozlovskaya, Dmitry Andreev, Andrey Aralov, Anna Varizhuk
Summary: Ribosomal frameshifting at the slippery site of SARS-CoV-2 RNA is crucial for viral replication, and inhibition of this process by oligonucleotide-based antivirals shows promise. In this study, locked nucleic acids (LNA) and other oligonucleotide analogs targeting the pseudoknot near the slippery site were shown to induce PK unfolding and inhibit frameshifting in a dose-dependent manner. These analogs also demonstrated the ability to reduce SARS-CoV-2 replication at subtoxic concentrations in human cell lines, highlighting their potential as antiviral agents.
Article
Multidisciplinary Sciences
Shuting Yan, Qiyao Zhu, Swati Jain, Tamar Schlick
Summary: This study investigates the conformation and mechanisms of action of the SARS-CoV-2 frameshifting element through the construction and simulation of multiple models. The findings provide new insights into frameshifting mechanisms and antiviral strategies.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Bayleigh E. Benner, James W. Bruce, Jacob R. Kentala, Magdalena Murray, Jordan T. Becker, Pablo Garcia-Miranda, Paul Ahlquist, Samuel E. Butcher, Nathan M. Sherer
Summary: This study reveals the mechanisms of Gag-Pol protein incorporation into HIV-1 virions. The study found that GP is enriched in virions about 3-fold compared to cells, and viral infectivity is better maintained at subphysiological levels of GP. It was also discovered that GP is more efficiently incorporated into virions when synthesized from the same mRNA as Gag. Furthermore, virions exhibit a strong upper limit to trans-delivered GP incorporation. These results provide new insights into the importance and regulation of GP in HIV-1 virion assembly.
JOURNAL OF VIROLOGY
(2022)
Article
Biology
Georgia M. Cook, Katherine Brown, Pengcheng Shang, Yanhua Li, Lior Soday, Adam M. Dinan, Charlotte Tumescheit, A. P. Adrian Mockett, Ying Fang, Andrew E. Firth, Ian Brierley
Summary: This study characterizes the transcriptome and translatome of the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV), and analyzes the host response to infection. The study reveals an increase in programmed ribosomal frameshift (PRF) efficiency over time at both viral genomic sites. Surprisingly, the study also finds an increase in PRF efficiency at the canonical ORF1ab frameshift site, contradicting the common assumption. Additionally, several highly translated additional viral ORFs and novel viral transcripts were discovered. These findings provide insights into the gene expression programs of PRRSV.
Article
Pharmacology & Pharmacy
Carmine Varricchio, Gregory Mathez, Trestan Pillonel, Claire Bertelli, Laurent Kaiser, Caroline Tapparel, Andrea Brancale, Valeria Cagno
Summary: Aminoglycoside antibiotic gentamicin has been found to effectively combat various variants of SARS-CoV-2 in different cell lines and respiratory tissue models. It inhibits viral RNA replication and protein expression at an early stage by targeting the ribosomal frameshift signal of SARS-CoV-2.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Howard Gamper, Isao Masuda, Ya-Ming Hou
Summary: This article summarizes recent research on +1-frameshifting tRNAs and suggests engineering the pairing scheme at steps after the A site in protein synthesis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemical Research Methods
Luke Trinity, Ian Wark, Lance Lansing, Hosna Jabbari, Ulrike Stege
Summary: Identifying inter-viral structural similarity in frameshifting pseudoknots is valuable for treatment development. We developed Shapify algorithm for improved prediction of possibly pseudoknotted RNA secondary structures. Our study sheds light on the structure formation of the SARS-CoV-2 and MERS-CoV frameshifting pseudoknots.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Cody J. Warren, Shuiqing Yu, Douglas K. Peters, Arturo Barbachano-Guerrero, Qing Yang, Bridget L. Burris, Gabriella Worwa, I-Chueh Huang, Gregory K. Wilkerson, Tony L. Goldberg, Jens H. Kuhn, Sara L. Sawyer
Summary: The study found that simian arteriviruses can use CD163 as an intracellular receptor to enter and replicate in human monocytes, indicating that they may not require major adaptations to infect human hosts. Given the potential fatal infections caused by simian arteriviruses in captive macaques and the lack of immunity in humans, developing serology tests for human surveillance should be a priority.
Article
Virology
Roman Kogay, Sonja Koppenhofer, J. Thomas Beatty, Jens H. Kuhn, Andrew S. Lang, Olga Zhaxybayeva
Summary: GTAs are entities that have evolved with cellular genomes and should not be considered viruses. Their lifecycles are analogous to viriforms found in parasitoid wasps.
Article
Pharmacology & Pharmacy
Jens H. Kuhn, Connie S. Schmaljohn
Summary: In 1998, the first immunocompetent laboratory mouse model of Ebola virus disease was developed by Mike Bray and colleagues. Despite being considered inferior to large nonhuman primate efforts initially, this model paved the way for the establishment of panel-derived cross-bred and humanized mouse models, as well as a golden hamster model. The global shortage of commercially available large nonhuman primates may lead to an increased focus on and improvement of rodent modeling, potentially replacing nonhuman primate studies in the short term and the future.
ANTIVIRAL RESEARCH
(2023)
Article
Microbiology
Guillermo Dominguez-Huerta, James M. Wainaina, Ahmed A. Zayed, Alexander I. Culley, Jens H. Kuhn, Matthew B. Sullivan
ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jens H. Kuhn, Eugene V. Koonin
Summary: The International Committee on Taxonomy of Viruses (ICTV) has recognized viriforms as a new category of virus-derived genetic elements, distinct from viruses, viroids, and satellite nucleic acids. Viriforms are former viruses that have been integrated into the genomes of cellular hosts and perform functions important for the host's life cycle. These viriforms resemble viruses in appearance but do not package their own genomes, instead transporting host genetic material. They have been found in the genomes of parasitoid wasps and prokaryotes, and recent discoveries suggest their presence in mammalian genomes. This article outlines the properties of different viriform groups and the proposed classification frameworks by ICTV.
Review
Biotechnology & Applied Microbiology
Stuart G. Siddell, Donald B. Smith, Evelien Adriaenssens, Poliane Alfenas-Zerbini, Bas E. Dutilh, Maria Laura Garcia, Sandra Junglen, Mart Krupovic, Jens H. Kuhn, Amy J. Lambert, Elliot J. Lefkowitz, Malgorzata Lobocka, Arcady R. Mushegian, Hanna M. Oksanen, David L. Robertson, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Nobuhiro Suzuki, Koenraad Van Doorslaer, Anne-Mieke Vandamme, Arvind Varsani, F. Murilo Zerbini
Summary: The International Committee on Taxonomy of Viruses (ICTV) is responsible for the development and oversight of virus taxonomy. It approves and ratifies taxonomic proposals and maintains a list of approved virus names. The ICTV has a democratic decision-making process with approximately 180 members who vote on proposals. Taxon-specific Study Groups, comprised of over 600 scientists, provide expertise and contribute to taxonomic proposals.
JOURNAL OF GENERAL VIROLOGY
(2023)
Editorial Material
Virology
Jens H. Kuhn, Steven B. Bradfute, Charles H. Calisher, Boris Klempa, Jonas Klingstrom, Lies Laenen, Gustavo Palacios, Connie S. Schmaljohn, Nicole D. Tischler, Piet Maes
Summary: The official classification of viruses by the ICTV requires complete or nearly complete genome sequences to be deposited in GenBank. This requirement is fairly new, resulting in fragmented or absent genomic sequence information for many classified viruses. This poses challenges for taxon-wide phylogenetic analyses, especially for viruses with segmented genomes. To address this issue for Hantaviridae, the community is urged to provide additional sequence information for incompletely sequenced classified viruses by mid-June 2023 to prevent possible declassification.
Article
Microbiology
Carla M. Bellomo, Daniel O. Alonso, Unai Perez-Sautu, Karla Prieto, Sebastian Kehl, Rocio M. Coelho, Natalia Periolo, Nicholas Di Paola, Natalia Ferressini-Gerpe, Jens H. Kuhn, Mariano Sanchez-Lockhart, Gustavo Palacios, Valeria P. Martinez
Summary: This study analyzed the Andes virus (ANDV) using whole-genome sequencing and identified four amino acid substitutions related to cell culture adaptation that attenuated the virus in an animal model. Additionally, three amino acid substitutions associated with efficient person-to-person transmission were identified. These findings suggest that single-nucleotide polymorphisms can be used to predict ANDV virulence and transmissibility.
Article
Microbiology
Jennifer Sword, Ji Hyun Lee, Marcelo A. A. Castro, Jeffrey Solomon, Nina Aiosa, Syed M. S. Reza, Winston T. T. Chu, Joshua C. C. Johnson, Christopher Bartos, Kurt Cooper, Peter B. B. Jahrling, Reed F. F. Johnson, Claudia Calcagno, Ian Crozier, Jens H. H. Kuhn, Lisa E. E. Hensley, Irwin M. M. Feuerstein, Venkatesh Mani
Summary: This study used CT imaging to identify abnormalities in the liver, spleen, and axillary lymph nodes that corresponded to the known clinical signs of Marburg virus disease in rhesus monkeys. The results suggest that CT imaging could be used to understand the pathogenesis of the disease and evaluate the effectiveness of candidate treatments.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Torsten Seuberlich, Jens H. H. Kuhn, Heike Schmidt-Posthaus
Summary: We obtained the near-complete genome sequence of a novel virus, Lotschberg virus (LTBV), from a European perch metatranscriptome. Genome organization and pairwise sequence comparison indicated that LTBV represents a tentative new species and genus of the mononegaviral family Filoviridae.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2023)
Article
Virology
Teressa M. Shaw, Sara M. Maloney, Kylie Nennig, Mitchell D. Ramuta, Andrew Norton, Rodrigo Ibarra, Paul Kuehnert, Margo Brinton, Kay Faaberg, Jens H. Kuhn, David H. O'Connor, Cody J. Warren, Adam L. Bailey
Summary: Arteriviruses, including lactate dehydrogenase-elevating virus (LDV), have been identified as RNA viruses related to coronaviruses. LDV is a valuable model for studying immune failure and viral persistence in immunocompetent mice. This study demonstrates that the macrophage marker CD163 is essential for LDV infection and the establishment of an immortalized cell-culture system. Additionally, LDV infection can be completely resisted in knockout mice lacking the expression of mCD163. The findings contribute to the understanding of arterivirus infection and highlight the significance of CD163 utilization in this virus family.
JOURNAL OF VIROLOGY
(2023)
Letter
Biotechnology & Applied Microbiology
Evelien M. M. Adriaenssens, Simon Roux, J. Rodney Brister, Ilene Karsch-Mizrachi, Jens H. H. Kuhn, Arvind Varsani, Tong Yigang, Alejandro Reyes, Cedric Lood, Elliot J. J. Lefkowitz, Matthew B. B. Sullivan, Robert A. A. Edwards, Peter Simmonds, Luisa Rubino, Sead Sabanadzovic, Mart Krupovic, Bas E. E. Dutilh
NATURE BIOTECHNOLOGY
(2023)
Correction
Biotechnology & Applied Microbiology
Evelien M. M. Adriaenssens, Simon Roux, J. Rodney Brister, Ilene Karsch-Mizrachi, Jens H. Kuhn, Arvind Varsani, Tong Yigang, Alejandro Reyes, Cedric Lood, Elliot J. Lefkowitz, Matthew B. B. Sullivan, Robert A. A. Edwards, Peter Simmonds, Luisa Rubino, Sead Sabanadzovic, Mart Krupovic, Bas E. E. Dutilh
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Todd A. Cutts, Raymond W. Nims, Joseph R. Rubino, Julie McKinney, Jens H. Kuhn, M. Khalid Ijaz
Summary: The World Health Organization's R & D Blueprint list includes Lassa fever as a priority disease for research and development in emergency contexts. The study evaluated the virucidal efficacy of various disinfectants against LASV and found rapid and substantial inactivation of the virus.
SCIENTIFIC REPORTS
(2023)
Review
Virology
Mohammad Fereidouni, Dmitry A. Apanaskevich, David B. Pecor, Natalia Yu. Pshenichnaya, Gulzhan N. Abuova, Farida H. Tishkova, Yekaterina Bumburidi, Xiankun Zeng, Jens H. Kuhn, Maryam Keshtkar-Jahromi
Summary: This study summarizes the status of Crimean-Congo hemorrhagic fever (CCHF) in Central, Eastern, and South-eastern Asia. The risk and burden of CCHF were assessed based on case reports, antibody prevalence, and vector ticks isolation. The majority of cases were reported in Central Asia, while only China reported cases in Eastern Asia. No cases were reported in South-eastern Asia. Countries were classified into different levels based on evidence of CCHF, guiding the strengthening or establishment of CCHF surveillance systems.