Article
Biochemistry & Molecular Biology
Sheng-Fan Wang, Yu-Hsien Hung, Ching-Han Tsao, Cho-Ying Chiang, Pak-Guan Teoh, Meng-Lin Chiang, Wei-Han Lin, Daniel K. Hsu, Hau-Ming Jan, Hsiu-Chu Lin, Chun-Hung Lin, Fu-Tong Liu, Huan-Yuan Chen
Summary: The study reveals that GAL3 promotes cell-to-cell transmission of HIV-1 in CD4 T cells by regulating lipid raft components. GAL3 is co-transferred with Gag to recipient cells and facilitates viral synapse formation at the cell-cell interface.
Article
Biochemistry & Molecular Biology
Maaran Michael Rajah, Mathieu Hubert, Elodie Bishop, Nell Saunders, Remy Robinot, Ludivine Grzelak, Delphine Planas, Jeremy Dufloo, Stacy Gellenoncourt, Alice Bongers, Marija Zivaljic, Cyril Planchais, Florence Guivel-Benhassine, Francoise Porrot, Hugo Mouquet, Lisa A. Chakrabarti, Julian Buchrieser, Olivier Schwartz
Summary: Severe cases of COVID-19 are associated with lung abnormalities, notably the presence of syncytial pneumocytes. New variants of the virus, such as Alpha and Beta, have shown an increased ability to form larger and more numerous syncytia compared to the ancestral strain D614G. The spike proteins of these variants also display higher affinity for the ACE2 receptor and can be inhibited by interferon-induced transmembrane proteins. Individual mutations in the spike proteins affect fusogenicity, ACE2 binding, and recognition by monoclonal antibodies. Additionally, the Delta variant spike protein has been found to trigger faster fusion than the D614G strain, indicating an enhanced syncytia formation capability in emerging SARS-CoV-2 variants.
Article
Biochemistry & Molecular Biology
Xuening Wang, Chih-Hsiung Chen, Saiaditya Badeti, Jong Hyun Cho, Alireza Naghizadeh, Ziren Wang, Dongfang Liu
Summary: The study investigated cell fusion events mediated by the S protein of SARS-CoV-2 and ACE2 interaction in different human cell lines, revealing that only certain cells expressing S protein can form syncytial structures. This cell-cell fusion process appears to be cell type-dependent and may rely on different parameters. The Delta 19-S variant shows defective nuclear fusion and syncytia formation compared to the wild-type S protein, which may have implications for pseudovirus-based entry assays and vaccine design strategies.
CELL AND BIOSCIENCE
(2021)
Review
Oncology
Thomas Dittmar, Julian Weiler, Tianjiao Luo, Ralf Hass
Summary: Cell fusion in cancer cells involving fusion proteins is a complex and energy-dependent process, potentially related to viruses and human endogenous retroviral elements. The phenomenon of multinucleation and fusion capacity may play a role in cancer initiation, progression, and metastasis, with syncytin-1 and enveloped viruses contributing to the fusion process. This review summarizes the potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion.
Article
Biochemistry & Molecular Biology
Bjoern-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Luebke, Maria Salgado, Kathleen Busman-Sahay, Jacob D. D. Estes, Laura E. P. Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Galvez, Christiane Mummert, Caroline Passaes, Johanna M. M. Eberhard, Carsten Muenk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gabor A. Dunay, Florian Klein, Dieter Haeussinger, Johannes C. C. Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Saez-Cirion, Julian Schulze zur Wiesch, Annemarie M. J. Wensing, Javier Martinez-Picado, Guido Kobbe
Summary: A 53-year-old male who received CCR5 Delta 32/Delta 32 hematopoietic stem cell transplantation for acute myeloid leukemia showed long-term remission of HIV-1. Despite sporadic traces of HIV-1 DNA, replication-competent virus was not detected in ex vivo and in vivo assays. Low levels of immune activation and declining HIV-1-specific immune responses indicated a lack of ongoing antigen production. After 4 years of treatment interruption, the absence of viral rebound and immunological correlates provide strong evidence for HIV-1 cure after CCR5 Delta 32/Delta 32 HSCT.
Article
Virology
Lili Wang, Alice Sandmeyer, Wolfgang Huebner, Hongru Li, Thomas Huser, Benjamin K. Chen
Summary: HIV-1 infection is enhanced by cell-cell adhesions called virological synapses (VS), in which infected and uninfected T cells interact. This study used a replication-competent HIV-1 clone to track the movement of HIV-1 envelope glycoprotein (Env) within infected cells. The results showed that Env was dynamically exchanged at the VS, while the viral structural protein, Gag, remained immobile. Further experiments revealed that continuous internalization and targeted secretion were involved in the accumulation of Env at the VS and its incorporation into nascent particles.
Review
Microbiology
Connie Zhao, Hongru Li, Talia H. Swartz, Benjamin K. Chen
Summary: The HIV Env glycoprotein plays a crucial role in viral entry and antibody responses. Complex mechanisms allow HIV-1 Env to evade the immune system. Env on infected cells has distinct conformations compared to Env on virus particles. Understanding these differences is essential for vaccine design and therapeutic strategies.
Review
Biochemistry & Molecular Biology
Maaran Michael Rajah, Annie Bernier, Julian Buchrieser, Olivier Schwartz
Summary: Syncytia play an important role in SARS-CoV-2 infection and pathology, potentially influencing the disease process through various mechanisms. Variants of concern have mutations in the S protein that enhance receptor interaction and fusogenicity. Several genes in the innate immune system act as barriers to syncytia formation. Understanding the fusogenicity of the Spike protein contributes to the understanding of SARS-CoV-2 infection and pathology.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shiu-Wan Chan
Summary: Virus fusion process is evolutionarily conserved and serves as a promising target for antiviral drugs. Researchers have developed fusion reporter gene assays to study plasma membrane and alternative fusion pathways, as well as syncytial fusion in SARS-CoV-2. They have identified potential novel fusion processes triggered by acidic pH, and discovered fusion inhibitors that could be used for therapeutics and elucidating the fusion process.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Behzad Etemad, Xiaoming Sun, Yijia Li, Meghan Melberg, Daniela Moisi, Rachel Gottlieb, Hayat Ahmed, Evgenia Aga, Ronald J. Bosch, Edward P. Acosta, Yuko Yuki, Maureen P. Martin, Mary Carrington, Rajesh T. Gandhi, Jeffrey M. Jacobson, Paul Volberding, Elizabeth Connick, Ronald Mitsuyasu, Ian Frank, Michael Saag, Joseph J. Eron, Daniel Skiest, David M. Margolis, Diane Havlir, Robert T. Schooley, Michael M. Lederman, Xu G. Yu, Jonathan Z. Li
Summary: This study evaluated the mechanisms of HIV post-treatment control and found that post-treatment controllers (PTCs) had stable HIV reservoirs and better immunological profiles. These findings have implications for future studies aiming at achieving an HIV functional cure.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Georg Jocher, Vincent Grass, Sarah K. Tschirner, Lydia Riepler, Stephan Breimann, Tugberk Kaya, Madlen Oelsner, M. Sabri Hamad, Laura Hofmann, Carl P. Blobel, Carsten B. Schmidt-Weber, Ozgun Gokce, Constanze A. Jakwerth, Jakob Trimpert, Janine Kimpel, Andreas Pichlmair, Stefan F. Lichtenthaler
Summary: Host metalloproteases ADAM10 and ADAM17 play important roles in facilitating SARS-CoV-2 cell entry and syncytia formation in lung cells, and are potential targets for antiviral drug development.
Article
Virology
Naoyuki Iida, Madoka Kawahara, Riku Hirota, Yoshio Shibagaki, Seisuke Hattori, Yuko Morikawa
Summary: The cell-cell contact between HIV-1-infected and uninfected cells forms a virological synapse (VS) to allow for efficient HIV-1 transmission. Mass spectrometry revealed the recruitment of various molecules, including ATP-related enzymes, protein translation factors, and charged multivesicular body protein 4B, to the VS. Further exploration showed that vimentin plays a role in HIV-1 transmission through the recruitment of CD4 to the cell-cell interface.
Article
Fisheries
Jemma V. Milburn, Anna M. Hoog, Simona Winkler, Katinka A. van Dongen, Judith Leitner, Martina Patzl, Armin Saalmueller, Karelle de Luca, Peter Steinberger, Kerstin H. Mair, Wilhelm Gerner
Summary: In this study, two novel monoclonal antibodies specific for porcine CD9 were reported. CD9 expression was found on a wide range of porcine immune cell subsets, with a correlation between CD9 expression and central memory CD4 T cells. The antibodies enable the detection of a cell surface molecule with functional relevance to T cells, benefiting swine biomedical research.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Immunology
Na Li, Xiao-Ling Chen, Qi Li, Zhe-Rui Zhang, Cheng-Lin Deng, Bo Zhang, Xiao-Dan Li, Han-Qing Ye
Summary: This study establishes a more convenient and efficient method for rapid screening of inhibitors blocking syncytium formation using VEEV-SARS-CoV-2-S-eGFP replicating cells. The assay can be performed in a BSL-2 laboratory without manipulation of live SARS-CoV-2.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Multidisciplinary Sciences
Daniel Ivanusic, Kazimierz Madela, Norbert Bannert, Joachim Denner
Summary: CD63, as a member of the tetraspanin superfamily, plays a central role in HIV-1 infection and pathogenesis by enhancing the formation of cell-to-cell virological synapse, which is crucial for persistent infection.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Adam W. Whisnant, Christopher S. Juerges, Thomas Hennig, Emanuel Wyler, Bhupesh Prusty, Andrzej J. Rutkowski, Anne L'hernault, Lara Djakovic, Margarete Goebel, Kristina Doering, Jennifer Menegatti, Robin Antrobus, Nicholas J. Matheson, Florian W. H. Kuenzig, Guido Mastrobuoni, Chris Bielow, Stefan Kempa, Chunguang Liang, Thomas Dandekar, Ralf Zimmer, Markus Landthaler, Friedrich Graesser, Paul J. Lehner, Caroline C. Friedel, Florian Erhard, Lars Doelken
NATURE COMMUNICATIONS
(2020)
Article
Biology
Sara Marelli, James C. Williamson, Anna Protasio, Adi Naamati, Edward J. D. Greenwood, Janet E. Deane, Paul J. Lehner, Nicholas J. Matheson
Article
Biology
Lucy Rivett, Sushmita Sridhar, Dominic Sparkes, Matthew Routledge, Nick K. Jones, Sally Forrest, Jamie Young, Joana Pereira-Dias, William L. Hamilton, Mark Ferris, M. Estee Torok, Luke Meredith, Martin D. Curran, Stewart Fuller, Afzal Chaudhry, Ashley Shaw, Richard J. Samworth, John R. Bradley, Gordon Dougan, Kenneth G. C. Smith, Paul J. Lehner, Nicholas J. Matheson, Giles Wright, Ian G. Goodfellow, Stephen Baker, Michael P. Weekes
Editorial Material
Multidisciplinary Sciences
Nicholas J. Matheson, Paul J. Lehner
Article
Biology
Allison N. Lau, Zhaoqi Li, Laura Danai, Anna M. Westermark, Alicia M. Darnell, Raphael Ferreira, Vasilena Gocheva, Sharanya Sivanand, Evan C. Lien, Kiera M. Sapp, Jared R. Mayers, Giulia Biffi, Christopher R. Chin, Shawn M. Davidson, David A. Tuveson, Tyler Jacks, Nicholas J. Matheson, Omer Yilmaz, Matthew G. Vander Heiden
Article
Biochemistry & Molecular Biology
Alba Luengo, Zhaoqi Li, Dan Y. Gui, Lucas B. Sullivan, Maria Zagorulya, Brian T. Do, Raphael Ferreira, Adi Naamati, Ahmed Ali, Caroline A. Lewis, Craig J. Thomas, Stefani Spranger, Nicholas J. Matheson, Matthew G. Vander Heiden
Summary: Increasing the activity of the pyruvate dehydrogenase complex impairs cell proliferation by reducing the NAD(+)/NADH ratio, which is caused by increased mitochondrial membrane potential. When demand for NAD(+) exceeds the demand for ATP in cells, aerobic glycolysis is promoted despite available oxygen.
Article
Immunology
Lior Soday, Martin Potts, Leah M. Hunter, Benjamin J. Ravenhill, Jack W. Houghton, James C. Williamson, Robin Antrobus, Mark R. Wills, Nicholas J. Matheson, Michael P. Weekes
Summary: This study reveals the variability of IFN alpha 2a effects among primary human immune cells, with differences in response observed between CD4+ T cells and monocytes. The research provides a comprehensive map of IFN alpha 2a-stimulated primary immune cell surface proteins and highlights the importance of understanding the impact of IFN on plasma membrane proteins for antiviral immunity and therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Nathaniel R. Campbell, Anjali Rao, Miranda Hunter, Magdalena K. Sznurkowska, Luzia Briker, Maomao Zhang, Maayan Baron, Silja Heilmann, Maxime Deforet, Colin Kenny, Lorenza P. Ferretti, Ting-Hsiang Huang, Sarah Perlee, Manik Garg, Jeremie Nsengimana, Massimo Saini, Emily Montal, Mohita Tagore, Julia Newton-Bishop, Mark R. Middleton, Pippa Corrie, David J. Adams, Roy Rabbie, Nicola Aceto, Mitchell P. Levesque, Robert A. Cornell, Itai Yanai, Joao B. Xavier, Richard M. White
Summary: Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that cooperate in the seeding of metastasis. INV cells tightly adhere to each other and form clusters with a rim of PRO cells, facilitating dissemination of less metastatic PRO cells. TFAP2 neural crest transcription factor is identified as a master regulator of clustering and PRO/INV states.
DEVELOPMENTAL CELL
(2021)
Article
Multidisciplinary Sciences
Arianna Baggiolini, Scott J. Callahan, Emily Montal, Joshua M. Weiss, Tuan Trieu, Mohita M. Tagore, Sam E. Tischfield, Ryan M. Walsh, Shruthy Suresh, Yujie Fan, Nathaniel R. Campbell, Sarah C. Perlee, Nathalie Saurat, Miranda Hunter, Theresa Simon-Vermot, Ting-Hsiang Huang, Yilun Ma, Travis Hollmann, Satish K. Tickoo, Barry S. Taylor, Ekta Khurana, Richard P. Koche, Lorenz Studer, Richard M. White
Summary: The intrinsic transcriptional program present in the cell of origin plays a key role in the transforming ability of oncogenes like BRAF(V600E), with developmental chromatin factors mediating oncogenic competence and allowing for proper response to oncogenes.
Article
Immunology
Bristy Sabikunnahar, Sydney Caldwell, Stella Varnum, Tyler Hogan, Alexei Cooper, Karolyn G. Lahue, Joseph J. Bivona, Phoebe M. Cousens, Menelaos Symeonides, Bryan A. Ballif, Matthew E. Poynter, Dimitry N. Krementsov
Summary: This study characterized a mouse long noncoding RNA named U90926. The expression of U90926 was induced in macrophages and dendritic cells by TLR activation. U90926 deficiency resulted in increased sickness responses and mortality in an endotoxic shock model, potentially mediated by the secreted U9-ORF protein.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Pehuen Pereyra Gerber, Maria J. Donde, Nicholas J. Matheson, Alexander Taylor
Summary: This study shows the design, synthesis, and screening of artificial RNA endonuclease XNAzymes capable of cleaving genomic SARS-CoV-2 RNA and self-assembling into enzymatic nanostructures inhibiting cellular viral replication.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Takayuki Hoshii, Sarah Perlee, Sota Kikuchi, Bahityar Rahmutulla, Masaki Fukuyo, Takeshi Masuda, Sumio Ohtsuki, Tomoyoshi Soga, Behnam Nabet, Atsushi Kaneda
Summary: The protein degrader technology was used in this study to degrade SETD1A and investigate its role in acute myeloid leukemia (AML) cells. The results showed that SETD1A degradation led to downregulation of DNA repair and heme biosynthesis pathways, and SETD1A was also found to be essential for maintaining mitochondrial respiration in AML cells. Furthermore, the study revealed a non-enzymatic role of SETD1A in transcriptional pause release, providing insight into the mechanism of RNA polymerase II (RNAPII) pausing and its function in cancer.
Article
Biochemistry & Molecular Biology
Sarah Perlee, Sota Kikuchi, Tomoyoshi Nakadai, Takeshi Masuda, Sumio Ohtsuki, Makoto Matsumoto, Bahityar Rahmutulla, Masaki Fukuyo, Paolo Cifani, Alex Kentsis, Robert G. Roeder, Atsushi Kaneda, Takayuki Hoshii
Summary: The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through the recruitment of cyclin K and regulation of DNA damage response genes. The FLOS domain of SETD1A interacts with mitosis-associated proteins BuGZ/BUB3 and inhibition of both cyclin K and BuGZ/BUB3-binding motifs in SETD1A shows synergistic antileukemic effects. BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions, and their interaction with SETD1A is required for leukemia cell proliferation.
Article
Oncology
Brandon J. Aubrey, Jevon A. Cutler, Wallace Bourgeois, Katherine A. Donovan, Shengqing Gu, Charlie Hatton, Sarah Perlee, Florian Perner, Homa Rahnamoun, Alexandra C. P. Theall, Jill A. Henrich, Qian Zhu, Radostaw P. Nowak, Young Joon Kim, Salma Parvin, Anjali Cremer, Sarah Naomi Olsen, Nicholas A. Eleuteri, Yana Pikman, Gerard M. McGeehan, Kimberly Stegmaier, Anthony Letai, Eric S. Fischer, X. Shirley Liu, Scott A. Armstrong
Summary: The combination targeting of IKAROS and MENIN is an effective therapeutic strategy for AML, disrupting leukemogenic transcriptional networks and resulting in synergistic killing of leukemia cells.
Article
Virology
Caroline C. Friedel, Adam W. Whisnant, Lara Djakovic, Andrzej J. Rutkowski, Marie-Sophie Friedl, Michael Kluge, James C. Williamson, Somesh Sai, Ramon Oliveira Vidal, Sascha Sauer, Thomas Hennig, Arnhild Grothey, Andrea Milic, Bhupesh K. Prusty, Paul J. Lehner, Nicholas J. Matheson, Florian Erhard, Lars Doelken
Summary: During the early stages of HSV-1 infection, the vhs protein cleaves host and viral mRNAs and decreases host transcriptional activity, leading to changes in RNA metabolism. While alterations in total RNA levels were mainly influenced by these global effects, gene-specific transcriptional changes were observed in chromatin-associated RNA.
JOURNAL OF VIROLOGY
(2021)