Article
Microbiology
Julia Mai, Miona Stubbe, Samuel Hofmann, Sawinee Masser, Thomas Dobner, Christopher Boutell, Peter Groitl, Sabrina Schreiner
Summary: PML-NB-associated factors could have beneficial effects on viral processes. Different PML isoforms have diverging roles in HAdV infection, with PML-II supporting viral progeny production and PML-III and PML-IV suppressing viral replication. PML-track formation plays a crucial role in efficient viral replication.
MICROBIOLOGY SPECTRUM
(2022)
Article
Virology
Samuel Hofmann, Miona Stubbe, Julia Mai, Sabrina Schreiner
Summary: PML nuclear bodies play a crucial role in virus infections by accumulating SUMO-dependent factors, which are targeted and manipulated by adenoviral proteins. Despite their antiviral reputation, Human Adenoviruses strategically utilize PML nuclear bodies for productive infection and oncogenic transformation, potentially counteracting antiviral responses while benefiting from or even depending on them.
Article
Microbiology
Lilian Goettig, Christina Weiss, Miona Stubbe, Lisa Hanrieder, Samuel Hofmann, Alessandro Grodziecki, Daniela Stadler, Arnaud Carpentier, Ulrike Protzer, Sabrina Schreiner
Summary: Apobec3A is upregulated during HAdV infection and its stabilization is mediated by viral proteins E1B-55K and E4orf6, leading to limited HAdV replication through a deaminase-dependent mechanism. Silencing Apobec3A enhances adenoviral replication. HAdV triggers Apobec3A dimerization and increases its activity to repress the virus by disrupting viral replication centers.
Article
Immunology
Natalie D. Collins, Shannon Beaty, Elana Wallace, Yuanzhang Li, Mark Sanborn, Yu Yang, Anima Adhikari, Paul Shabram, Kelly Warfield, Nicos Karasavvas, Robert A. Kuschner, Jun Hang
Summary: The FDA-approved Adenovirus Type 4 and Type 7 Vaccine is highly effective in preventing acute respiratory diseases in U.S. military recruits. Our study found a previously undetected mutation in the component of the licensed vaccine, which may affect vaccine efficacy as it favors replication in certain cells but declines in the gastrointestinal tract.
Article
Microbiology
Jana Boddin, Wing-Hang Ip, Britta Wilkens, Konstantin von Stromberg, Wilhelm Ching, Emre Koyuncu, Luca D. Bertzbach, Thomas Dobner
Summary: This study reveals the significant impact of single amino acid exchange mutations in the DNA binding protein of human adenovirus on viral replication. The interactions with the cellular ubiquitination machinery and the formation of viral replication centers are crucial steps that are affected by these mutations. This research has implications for the optimization of adenoviral vectors and the development of anti-adenoviral compounds.
Article
Virology
Yuqian Yan, Shuping Jing, Liqiang Feng, Jing Zhang, Zhiwei Zeng, Min Li, Shan Zhao, Junxian Ou, Wendong Lan, Wenyi Guan, Xiaowei Wu, Jianguo Wu, Donald Seto, Qiwei Zhang
Summary: HAdVs cause a large number of ARD cases with severe morbidity and mortality, and HAdV-3 is the most common type causing outbreaks. This study constructed a novel recombinant and attenuated adenovirus vaccine candidate against HAdV-3, showing promising safety and efficacy in experiments.
Article
Virology
Linlin Zhang, Yali Duan, Wei Wang, Qi Li, Jiao Tian, Yun Zhu, Ran Wang, Zhengde Xie
Summary: HAdV-B7 infection induces complete autophagic flux, and pharmacological induction of autophagy inhibits HAdV-B7 replication. Host protein BAG3 mediates autophagy to inhibit HAdV-B7 replication by binding to the PPSY structural domain of viral protein pVI.
Article
Virology
Paloma Hidalgo, Arturo Pimentel, Diana Mojica-Santamaria, Konstantin von Stromberg, Helga Hofmann-Sieber, Christian Lona-Arrona, Thomas Dobner, Ramon A. Gonzalez
Summary: During viral infection, the formation of intracellular replication compartments that exhibit liquid biomolecular condensate properties has been observed. These compartments can fuse, divide, and eventually form mesh-like structures in the nucleus. The results suggest that the viral ssDNA-binding protein may play a key role in assembly and properties of these compartments, and contribute to future studies on virus-host cell interactions.
Article
Biochemistry & Molecular Biology
Emile Alghoul, Matteo Paloni, Arato Takedachi, Serge Urbach, Alessandro Barducci, Pierre-Henri Gaillard, Jihane Basbous, Angelos Constantinou
Summary: SLX4 is a scaffolding protein that coordinates the action of structure-specific endonucleases and other proteins involved in the replication-coupled repair of DNA interstrand cross-links. It forms membraneless compartments called condensates in the nucleus through dimerization and SUMO-SIM interactions. These condensates compartmentalize proteins, such as the SUMO-RNF4 signaling pathway, and regulate protein modifications and nucleolytic reactions during DNA repair.
Article
Virology
Marie Fiedler, Wing-Hang Ip, Helga Hofmann-Sieber, Britta Wilkens, Francis K. Nkrumah, Wenli Zhang, Anja Ehrhardt, Luca D. Bertzbach, Thomas Dobner
Summary: The human adenovirus type C5 (HAdV-C5) E1B-55K protein is a multifunctional regulator of HAdV-C5 replication, with phosphorylation and SUMO conjugation playing important roles in its functions. The interaction between E1B-55K and E4orf6 inhibits SUMOylation of E1B-55K, which may promote viral replication.
Article
Virology
Viktoria Kolbe, Wing H. Ip, Lisa Kieweg-Thompson, Judith Lang, Julia Gruhne, Tina Meyer, Britta Wilkens, Marcel Schie, Roland Thunauer, Sabrina Schreiner, Luca D. Bertzbach, Estefania Rodriguez, Thomas Dobner
Summary: This research identified potential SUMO-conjugation motifs in E1B-55K proteins from HAdV species A to F and demonstrated that these proteins are SUMOylated at a highly conserved lysine residue. The study also revealed that E1B-55K SUMOylation regulates intracellular localization and p53-mediated transcription in most HAdV species.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Samuel Hofmann, Miona Stubbe, Julia Mai, Sabrina Schreiner
Summary: PML nuclear bodies play a crucial role in virus infections by accumulating SUMO-dependent factors, which are targeted and manipulated by adenoviral proteins. Despite their antiviral reputation, Human Adenoviruses strategically utilize PML nuclear bodies for productive infection and oncogenic transformation, potentially counteracting antiviral responses while benefiting from or even depending on them.
Article
Medicine, Research & Experimental
Goetz Hartleben, Kenji Schorpp, Yun Kwon, Barbara Betz, Foivos-Filippos Tsokanos, Zahra Dantes, Arlett Schaefer, Ina Rothenaigner, Jose Manuel Monroy Kuhn, Pauline Morigny, Lisa Mehr, Sean Lin, Susanne Seitz, Janina Tokarz, Anna Artati, Jerzy Adamsky, Oliver Plettenburg, Dominik Lutter, Martin Irmler, Johannes Beckers, Maximilian Reichert, Kamyar Hadian, Anja Zeigerer, Stephan Herzig, Mauricio Berriel Diaz
Summary: By emphasizing drug efficacy and inhibiting resistance mechanisms, combinatorial therapies have emerged as a key approach in complex disease treatment, particularly cancer. Through high-throughput drug screens, researchers identified metabolic vulnerabilities in tumor cells, leading to a combinatorial response that induced cell death through enhanced pyrimidine catabolism and reduced pyrimidine synthesis. This approach sensitized human organoid cultures to standard chemotherapy and could potentially be implemented into established treatment regimens, with the added benefit of drug repurposing.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell & Tissue Engineering
Vidya Padmanabhan Nair, Hengyuan Liu, Gabriele Ciceri, Johannes Jungverdorben, Goar Frishman, Jason Tchieu, Gustav Y. Cederquist, Ina Rothenaigner, Kenji Schorpp, Lena Klepper, Ryan M. Walsh, Tae Wan Kim, Daniela Cornacchia, Andreas Ruepp, Jens Mayer, Kamyar Hadian, Dmitrij Frishman, Lorenz Studer, Michelle Vincendeau
Summary: Elevated HERV-K (HML-2) transcription is detrimental to the development and function of cortical neurons, with dopaminergic neurons being unaffected. The effects are associated with hyperactivation of NTRK3 expression, revealing a cell-type-specific role for HERV-K (HML-2) in cortical neuron development.
Review
Biochemical Research Methods
Ina Rothenaigner, Kamyar Hadian
Summary: Small-molecule screening is a powerful method for identifying modulators of biological targets, but hit compounds causing assay interference can lead to false positives. Computational and experimental approaches are essential for flagging and eliminating unwanted compounds to prioritize high-quality hits for further analysis.
Editorial Material
Immunology
Emma L. Poole, Michael M. Nevels
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Forstner, Sean Lin, Xiaohua Yang, Susanna Kinting, Ina Rothenaigner, Kenji Schorpp, Yang Li, Kamyar Hadian, Matthias Griese
Summary: ABCA3 gene mutations are a common cause of respiratory distress syndrome and interstitial lung disease. There is currently no cure for ABCA3 deficiency. Researchers developed a cell-based assay and used machine learning algorithms to identify and study mutant cells, with the aim of finding therapeutic options.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Dipan Ghosh, Uwe Koch, Kamyar Hadian, Michael Sattler, Igor V. Tetko
Summary: AlphaScreen is a widely used assay technology in drug discovery, but faces challenges with false positives and frequent hitters. Traditional scaffold-based filters are time-consuming to develop, while machine learning methods provide more accurate and easily updatable filters for identification of frequent hitters.
MOLECULAR INFORMATICS
(2022)
Correction
Biochemistry & Molecular Biology
Ane Iturbide, Mayra L. Ruiz Tejada Segura, Camille Noll, Kenji Schorpp, Ina Rothenaigner, Elias R. Ruiz-Morales, Gabriele Lubatti, Ahmed Agami, Kamyar Hadian, Antonio Scialdone, Maria-Elena Torres-Padilla
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Virology
Maria Soderlund-Venermo, Anupam Varma, Deyin Guo, Douglas P. Gladue, Emma Poole, Flor H. Pujol, Hanu Pappu, Jesus L. Romalde, Laura Kramer, Mariana Baz, Marietjie Venter, Matthew D. Moore, Michael M. Nevels, Sayeh Ezzikouri, Vikram N. Vakharia, William C. Wilson, Yashpal S. Malik, Zhengli Shi, Ahmed S. Abdel-Moneim
Summary: This article summarizes the presentations given at the 1st international conference of the World Society for Virology (WSV). The conference focused on tackling global viral epidemics and aimed to foster international collaborations. The conference consisted of multiple sessions and attracted 270 scientists from 49 countries.
Article
Biochemistry & Molecular Biology
Jenny Jin, Kenji Schorpp, Daniel Samaga, Kristian Unger, Kamyar Hadian, Brent R. Stockwell
Summary: A machine learning approach combined with staining techniques was developed to unbiasedly classify different cell death mechanisms based on specific cell features, providing a novel analytic framework.
ACS CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Julia Mai, Miona Stubbe, Samuel Hofmann, Sawinee Masser, Thomas Dobner, Christopher Boutell, Peter Groitl, Sabrina Schreiner
Summary: PML-NB-associated factors could have beneficial effects on viral processes. Different PML isoforms have diverging roles in HAdV infection, with PML-II supporting viral progeny production and PML-III and PML-IV suppressing viral replication. PML-track formation plays a crucial role in efficient viral replication.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Simone Queiroz Pantaleao, Livia de Moraes Bomediano Camillo, Tainan Cerqueira Neves, Isabela de Godoy Menezes, Lucas Matheus Stangherlin, Helena Beatriz de Carvalho Ruthner Batista, Emma Poole, Michael Nevels, Eric Alisson Philot, Ana Ligia Scott, Maria Cristina Carlan da Silva
Summary: This study investigates the expression spectrum and structure of different isoforms encoded by the UL111A gene of human cytomegalovirus (HCMV), as well as their interactions with the human interleukin 10 receptor. Molecular modeling predicts structural differences and different molecular interactions between isoforms. Understanding specific viral IL-10 isoforms is important for understanding their role in HCMV immune evasion and pathogenesis.
Review
Biotechnology & Applied Microbiology
Kamyar Hadian, Brent R. R. Stockwell
Summary: This article introduces the regulation of non-apoptotic cell death, such as necroptosis, pyroptosis, parthanatos, and ferroptosis, and provides an update on the development of small-molecule inhibitors targeting these pathways. Cell death is critical for the development and homeostasis of multicellular organisms, and dysregulation can lead to various diseases. Recent research has uncovered regulated forms of necrosis that are associated with degenerative diseases, inflammation, and cancer. Understanding these pathways offers new opportunities for therapeutic targeting.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Cell Biology
Kenji Schorpp, Alaa Bessadok, Aidin Biibosunov, Ina Rothenaigner, Stefanie Strasser, Tingying Peng, Kamyar Hadian
Summary: Cell death, including apoptosis and ferroptosis, plays a crucial role in development, homeostasis, and the pathogenesis of diseases. The ability to modulate different cell death types offers promising therapeutic opportunities. However, identifying specific cell death types is a challenging task that requires computational analysis and costly experimental assays. In this study, we introduce CellDeathPred, a deep-learning framework that uses high-content imaging to distinguish between ferroptotic or apoptotic cells and healthy cells. Our framework effectively embeds microscopic images and classifies them into different cell death modalities, providing a new tool for cell death discovery and research.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Valeria Napolitano, Agnieszka Dabrowska, Kenji Schorpp, Andre Mourao, Emilia Barreto-Duran, Malgorzata Benedyk, Pawel Botwina, Stefanie Brandner, Mark Bostock, Yuliya Chykunova, Anna Czarna, Grzegorz Dubin, Tony Froehlich, Michael Hoelscher, Malwina Jedrysik, Alex Matsuda, Katarzyna Owczarek, Magdalena Pachota, Oliver Plettenburg, Jan Potempa, Ina Rothenaigner, Florian Schlauderer, Klaudia Slysz, Artur Szczepanski, Kristin Greve-Isdahl Mohn, Bjorn Blomberg, Michael Sattler, Kamyar Hadian, Grzegorz Maria Popowicz, Krzysztof Pyrc
Summary: Acriflavine has been identified as a potent inhibitor of viral replication in SARS-CoV-2 and other betacoronaviruses, with potential for immediate use in clinical trials and future outbreaks.
CELL CHEMICAL BIOLOGY
(2022)