Article
Microbiology
Alice Duchon, Steven Santos, Jianbo Chen, Matthew Brown, Olga A. Nikolaitchik, Sheldon Tai, Jeffrey A. Chao, Eric O. Freed, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 Gag selects and packages the HIV RNA genome during virus assembly, with multimerization and plasma membrane anchoring properties playing critical roles in efficient genome packaging. Studying these properties can provide insights into the mechanisms of viral RNA packaging and assembly of infectious virions.
Article
Virology
Silvia A. Gonzalez, Jose L. Affranchino
Summary: Mutations C33S and R7A/K8A impair virion assembly and viral RNA binding, while mutations C12S and R29A/R30A allow substantial particle production and genomic RNA encapsidation. These findings help define the relative contribution of the SIV NC zinc finger motifs and basic regions to the NC biological properties.
Article
Biochemistry & Molecular Biology
L. B. P. Socas, E. E. Ambroggio
Summary: HIV-1 assembly is guided by the Gag polyprotein, which interacts with the plasma membrane through the matrix domain (MA). The presence of phosphatidylinositol(4,5)-bisphosphate (PIP2) is believed to significantly influence this binding. Additionally, RNA is hypothesized to have a chaperone function by interacting with MA, preventing unspecific association of Gag with lipid interfaces.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Article
Microbiology
Han Xiao, Emanuel Wyler, Miha Milek, Bastian Grewe, Philipp Kirchner, Arif Ekici, Ana Beatriz Oliveira Villela Silva, Doris Jungnickl, Florian Full, Marco Thomas, Markus Landthaler, Armin Ensser, Klaus Ueberla
Summary: The HIV-1 Rev protein is crucial for nuclear export of unspliced and incompletely spliced HIV-1 RNAs. Depletion of proteins like CRNKL1 can significantly enhance levels of unspliced HIV-1 RNA in the cytoplasm, potentially revealing a cellular mechanism exploited by HIV-1 to regulate its complex splicing pattern.
Article
Virology
Madushi Wanaguru, Kate N. Bishop
Summary: The p12 protein of MLV and the p6 protein of HIV-1 are both supplementary Gag cleavage products that carry proline-rich motifs facilitating virus budding. While p12 is essential for early viral replication events, the role of Vpr and mature p6 in early replication remains unclear. Mutagenesis studies suggest that p6 is not crucial for early viral replication, with most mature p6 and recruited Vpr being rapidly lost upon target cell entry.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuki Furuse
Summary: Recent studies have shown the importance of RNA modifications in cellular functions, but information about RNA modifications in viral RNA is limited. Influenza A virus infection affects the expression levels of host factors for RNA modifications, some of which may have a proviral effect. This novel aspect of host-virus interactions could lead to the discovery of previously unrecognized viral pathogenicity mechanisms and aid in the development of new antiviral drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Fathima Nuzra Nagoor Pitchai, Akhil Chameettachal, Valerie Vivet-Boudou, Lizna Mohamed Ali, Vineeta N. Pillai, Anjana Krishnan, Serena Bernacchi, Farah Mustafa, Roland Marquet, Tahir A. Rizvi
Summary: In this study, retroviral Gag proteins were found to select gRNA against spliced viral RNA by simultaneously binding to two single stranded loops on the MPMV Psi RNA. The second Gag binding site, crucial for MPMV gRNA packaging, is located immediately downstream of the major splice donor.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Virology
John M. M. Crawford, Liewei L. L. Yan, Hani Zaher, Richard W. W. Hardy
Summary: Virus replication and transmission vary between different hosts. Mosquito-derived Sindbis virus (SINV) replicates and spreads faster in human cells, producing a more infectious virus than its mammalian-derived counterpart. The genomic RNA of mosquito-derived SINV is more efficient in establishing infection in human cells compared to that of mammalian-derived SINV. Host-dependent changes in modification of packaged genomic RNA likely play an important role in SINV infection and replication.
Article
Multidisciplinary Sciences
Gatikrushna Singh, Bradley Seufzer, Zhenwei Song, Dora Zucko, Xiao Heng, Kathleen Boris-Lawrie
Summary: This study reveals the relationship between incomplete processing and hypermethylation of HIV-1 transcripts, as well as the role of trimethylguanosine synthetase-1 in HIV-1 infectivity and protein synthesis. The study also uncovers the interaction between nuclear RNA helicase A and the shape of the 5' untranslated region primer binding site, and the relationship between HIV-1 virion protein synthesis and host translation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Analytical
Kiara Lee, John Murphy, Anubhav Tripathi
Summary: This study developed a DBS extraction method using the synergistic action of electrophoretic and diffusive transport mechanisms to extract high-quality gDNA in just 5 minutes, without the need for heat, shaking, and DNA purification steps. The method is suitable for point of care and automation.
ANALYTICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Akhil Chameettachal, Farah Mustafa, Tahir A. Rizvi
Summary: Members of the Retroviridae family are important pathogens in animals and humans. The replication of retroviruses involves multiple unique steps, such as reverse transcription, integration, and specific packaging of their genomic RNA. Although progress has been made in understanding the molecular mechanisms of these steps, many aspects remain unknown or controversial. This review provides a comprehensive analysis of our current understanding of retrovirus replication and RNA packaging, highlighting the interplay between viral and cellular factors and exploring areas for further research.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Barbara Szutkowska, Klaudia Wieczorek, Ryszard Kierzek, Pawel Zmora, Jake M. Peterson, Walter N. Moss, David H. Mathews, Elzbieta Kierzek
Summary: This study proposes a secondary structure for segment 8 vRNA of A/California/04/2009 (H1N1) for the first time and highlights the location of conserved structural motifs within IAV strains. The research has implications for understanding the functionality of viral RNA structures and developing inhibition methods against influenza A virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Kannan Balakrishnan, Ananda Ayyappan Jaguva Vasudevan, Krishnaveni Mohareer, Tom Luedde, Carsten Muenk, Sharmistha Banerjee
Summary: The study showed that Staufen-2 interacts with HIV-1 Gag, boosting viral infectivity by being incorporated into virions. Additionally, Staufen-2 may interact with other host factors, influencing the infectivity and population dynamics of the virus.
Review
Virology
Heather M. Hanson, Nora A. Willkomm, Huixin Yang, Louis M. Mansky
Summary: This review provides an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses, specifically HIV-1, HIV-2, and HTLV-1, which cause diseases in humans. It focuses on the genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.
Review
Microbiology
Mathieu Long, Johan Toesca, Christophe Guillon
Summary: The Gag polyprotein plays crucial roles in the budding and replication of retroviruses, with structural data on FIV Gag subunits emerging in recent years. Understanding the structure-function relationships is essential for developing anti-FIV molecules.
Article
Immunology
Juliane Fornefett, Jaqueline Krause, Kristin Klose, Felix Fingas, Rayk Hassert, Tobias Eisenberg, Wieland Schroedl, Thomas Grunwald, Uwe Mueller, Christoph G. Baums
MICROBES AND INFECTION
(2018)
Article
Multidisciplinary Sciences
Lea Bayer, Jessica Guempel, Gerd Hause, Martin Mueller, Thomas Grunwald
Article
Immunology
Lea Bayer, Jasmin Fertey, Sebastian Ulbert, Thomas Grunwald
Article
Biochemical Research Methods
Felix Fingas, Antje Rueckner, Kristin Heenemann, Daniela Volke, Michael Sieg, Petra Bielefeldt, Thomas Grunwald, Thomas W. Vahlenkamp, Rayk Hassert, Ralf Hoffmann
JOURNAL OF VIROLOGICAL METHODS
(2018)
Article
Immunology
Sarah Wilmschen, Sabrina Schneider, Felix Peters, Lea Bayer, Leila Issmail, Zoltan Banki, Thomas Grunwald, Dorothee von Laer, Janine Kimpel
Article
Multidisciplinary Sciences
Jasmin Fertey, Martin Thoma, Jana Beckmann, Lea Bayer, Julia Finkensieper, Susann Reisshauer, Beatrice Sarah Berneck, Leila Issmail, Jessy Schoenfelder, Javier Portillo Casado, Andre Poremba, Frank-Holm Roegner, Bastian Standfest, Gustavo R. Makert, Lia Walcher, Ann-Kathrin Kistenmacher, Stephan Fricke, Thomas Grunwald, Sebastian Ulbert
SCIENTIFIC REPORTS
(2020)
Article
Immunology
Beatrice Sarah Berneck, Alexandra Rockstroh, Jasmin Fertey, Thomas Grunwald, Sebastian Ulbert
Article
Immunology
Antonia Sophia Peter, Edith Roth, Sebastian R. Schulz, Kirsten Fraedrich, Tobit Steinmetz, Dominik Damm, Manuela Hauke, Elie Richel, Sandra Mueller-Schmucker, Katharina Habenicht, Valentina Eberlein, Leila Issmail, Nadja Uhlig, Simon Dolles, Eva Gruner, David Peterhoff, Sandra Ciesek, Markus Hoffmann, Stefan Pohlmann, Paul F. McKay, Robin J. Shattock, Roman Wolfel, Eileen Socher, Ralf Wagner, Jutta Eichler, Heinrich Sticht, Wolfgang Schuh, Frank Neipel, Armin Ensser, Dirk Mielenz, Matthias Tenbusch, Thomas H. Winkler, Thomas Grunwald, Klaus Uberla, Hans-Martin Jack
Summary: TRIANNI mice were used to generate 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein, and identified two clusters of neutralizing antibodies targeting different regions of the spike protein. These neutralizing antibodies significantly reduced viral spread and protected mice from SARS-CoV-2-induced weight loss, showing potential for therapy and prophylaxis of COVID-19.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Christian Gege, Fernando J. Bravo, Nadja Uhlig, Timo Hagmaier, Rosanne Schmachtenberg, Julia Elis, Anke Burger-Kentischer, Doris Finkelmeier, Klaus Hamprecht, Thomas Grunwald, David Bernstein, Gerald Kleymann
Summary: The text discusses the high prevalence of chronic herpesvirus infections and introduces a new HSV helicase-primase inhibitor, IM-250, with potential in vitro anti-herpes activity. IM-250 shows advantages over standard-of-care therapies in reducing disease duration, preventing recurrence, and maintaining effectiveness post-treatment cessation.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Nadja Uhlig, Anne-Kathrin Donner, Christian Gege, Franziska Lange, Gerald Kleymann, Thomas Grunwald
Summary: The novel HPI compounds showed superior antiviral efficacy compared to the current standard HSV treatment represented by VACV in terms of survival rates, clinical scores, and reductions in viral load in the lungs and brains. These new drug candidates are promising for the treatment of HSV infections and warrant further translation into clinical trials.
ANTIVIRAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Dennis Lapuente, Jana Fuchs, Jonas Willar, Ana Vieira Antao, Valentina Eberlein, Nadja Uhlig, Leila Issmail, Anna Schmidt, Friederike Oltmanns, Antonia Sophia Peter, Sandra Mueller-Schmucker, Pascal Irrgang, Kirsten Fraedrich, Andrea Cara, Markus Hoffmann, Stefan Poehlmann, Armin Ensser, Cordula Pertl, Torsten Willert, Christian Thirion, Thomas Grunwald, Klaus Ueberla, Matthias Tenbusch
Summary: The study demonstrates that priming with systemic mRNA and boosting with intranasal adenoviral vector vaccine in mice induces comprehensive T cell and mucosal immunity. The strategy provides complete protection against SARS-CoV-2 infection in mice after boosting.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Rudiger Gross, Livia Mesquita Dias Loiola, Leila Issmail, Nadja Uhlig, Valentina Eberlein, Carina Conzelmann, Lia-Raluca Olari, Lena Rauch, Jan Lawrenz, Tatjana Weil, Janis A. Mueller, Mateus Borba Cardoso, Andrea Gilg, Olivia Larsson, Urban Hoeglund, Sandra Axberg Palsson, Anna Selch Tvilum, Kaja Borup Lovschall, Maria M. Kristensen, Anna-Lena Spetz, Fortune Hontonnou, Marie Galloux, Thomas Grunwald, Alexander N. Zelikin, Jan Munch
Summary: This study investigates the use of poly(styrene sulfonate)-based inhibitors and core-shell nanoformulations based on gold nanoparticles against a range of viruses, including SARS-CoV-2. The macromolecular inhibitors show broad-spectrum antiviral activity and effectively inhibit enveloped respiratory viruses. The findings provide valuable insights into the development of antiviral drugs.
Article
Immunology
Julia Finkensieper, Leila Issmail, Jasmin Fertey, Alexandra Rockstroh, Simone Schopf, Bastian Standfest, Martin Thoma, Thomas Grunwald, Sebastian Ulbert
Summary: Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus that can cause severe neurological complications in humans. Traditional methods of producing TBEV vaccines using formaldehyde have drawbacks, and this study suggests that low-energy electron irradiation (LEEI) could be an alternative method. Immunizing mice with LEEI-inactivated TBEV resulted in higher levels of antibodies and complete protection against viral challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kim M. Stegmann, Antje Dickmanns, Natalie Heinen, Claudia Blaurock, Tim Karrasch, Angele Breithaupt, Robert Klopfleisch, Nadja Uhlig, Valentina Eberlein, Leila Issmail, Simon T. Herrmann, Amelie Schreieck, Evelyn Peelen, Hella Kohlhof, Balal Sadeghi, Alexander Riek, John R. Speakman, Uwe Gross, Dirk Gorlich, Daniel Vitt, Thorsten Muller, Thomas Grunwald, Stephanie Pfaender, Anne Balkema-Buschmann, Matthias Dobbelstein
Summary: This study demonstrates a strong synergy between the nucleoside analog N4-hydroxycytidine (NHC) and inhibitors of dihydroorotate dehydrogenase (DHODH) in inhibiting the replication of SARS-CoV-2. Inhibition of DHODH increases the incorporation of NHC into viral RNA, leading to defective virus genomes. The combination of NHC and DHODH inhibitors may improve therapy options for COVID-19.
Article
Chemistry, Multidisciplinary
Tatjana Weil, Abbna Kirupakaran, My-Hue Le, Philipp Rebmann, Joel Mieres-Perez, Leila Issmail, Carina Conzelmann, Janis A. Mueller, Lena Rauch, Andrea Gilg, Lukas Wettstein, Ruediger Gross, Clarissa Read, Tim Bergner, Sandra Axberg Palsson, Nadja Uhlig, Valentina Eberlein, Heike Woell, Frank-Gerrit Klaerner, Steffen Stenger, Beate M. Kuemmerer, Hendrik Streeck, Giorgio Fois, Manfred Frick, Peter Braubach, Anna-Lena Spetz, Thomas Grunwald, James Shorter, Elsa Sanchez-Garcia, Thomas Schrader, Jan Muench
Summary: This study discovered that a class of drugs called molecular tweezers can disrupt the envelope of SARS-CoV-2 and render the virus non-infectious. By modifying the molecular structure, researchers identified a series of advanced molecular tweezers that showed enhanced ability to destroy lipid bilayers and suppress SARS-CoV-2 infection. These potentiated tweezers demonstrated activity against various viruses, including respiratory syncytial virus, influenza, and measles viruses, in addition to SARS-CoV-2. The inhibitory effects of the advanced tweezers against respiratory syncytial virus and SARS-CoV-2 were also validated in mice. Therefore, these broad-spectrum antiviral agents have great potential for clinical development in combating highly pathogenic viruses.