Article
Multidisciplinary Sciences
Elizabeth B. Draganova, Ekaterina E. Heldwein
Summary: Herpesviruses infect a majority of the human population, establishing lifelong latent infections with no cure, and periodic viral reactivation spreads infection while causing disease states that are particularly harmful in the immunocompromised. The viral replication and spread of infection rely on the nuclear egress complex (NEC), which helps translocate viral capsids and mature them into infectious virions. Peptides derived from the UL25 capsid protein have been shown to inhibit the membrane-budding activity of the NEC, providing a potential new avenue for developing inhibitors against herpesvirus replication.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Masoudeh Masoud Bahnamiri, Richard J. Roller
Summary: The study found that disruption of the nuclear lamina and changes in lamina structure can occur without capsid envelopment, suggesting that the disruption of the nuclear lamina may precede capsid envelopment. In the absence of capsid envelopment, the virus-encoded protein kinase pUS3 may regulate nuclear egress through controlling NEC self-association and membrane deformation.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Amber Vu, Shaowen White, Tiffany Cassmann, Richard J. Roller
Summary: Herpesvirus nuclear egress involves a regulated process coordinated by two virus proteins, with a heterodimeric nuclear egress complex (NEC) that drives budding of capsids at the inner nuclear membrane. Mutants with unregulated budding phenotype were studied, showing the significance of this regulation for virus replication and a structural requirement for nuclear lamina disruption.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Jun Arii, Kosuke Takeshima, Yuhei Maruzuru, Naoto Koyanagi, Yoshitaka Nakayama, Akihisa Kato, Yasuko Mori, Yasushi Kawaguchi
Summary: This study identifies an arginine cluster in the disordered domain of UL34 that interacts with ALIX and recruits ESCRT-III machinery for primary envelopment. The study highlights the importance of the disordered domain of UL34 in herpesvirus infections.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Nabil El Bilali, Bita Khadivjam, Eric Bonneil, Pierre Thibault, Roger Lippe
Summary: The study investigated the composition of HSV-1 A, B, and C nuclear capsids, identifying host proteins specific to C-capsids. By purifying viral particles using a novel method, it aims to uncover the differences and functional relevance of these viral capsids. This innovative approach opens up new research avenues to clarify the biology of herpesviruses.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Richard J. Roller, Tineke Hassman, Alison Haugo-Crooks
Summary: The study found that substituting the HSV-1 UL34 coding sequence with VZV ORF24 resulted in viral defects in growth and spread, despite normal protein interaction and localization. Cell culture evolution showed that the mutated viruses grew and spread more efficiently, revealing the important roles of ICP22 and ICP4 in nuclear lamina disruption and capsid nuclear egress.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Fumio Maeda, Akihisa Kato, Kosuke Takeshima, Misato Shibazaki, Ryota Sato, Takuma Shibata, Kensuke Miyake, Hiroko Kozuka-Hata, Masaaki Oyama, Eigo Shimizu, Seiya Imoto, Satoru Miyano, Shungo Adachi, Tohru Natsume, Koh Takeuchi, Yuhei Maruzuru, Naoto Koyanagi, Arii Jun, Kawaguchi Yasushi
Summary: This study developed a screening system to identify cellular proteins involved in the nuclear egress of HSV-1. Through this system, the researchers discovered that the cellular orphan transporter SLC35E1 plays a critical role in HSV-1 de-envelopment.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Fujun Hou, Zeyu Sun, Yue Deng, Siyu Chen, Xiyuan Yang, Feiyang Ji, Menghao Zhou, Keyi Ren, Dongli Pan
Summary: This study investigates the targets of ICP0 in HSV-1 infection and its roles in neuronal cells. Mass spectrometry analysis identified various proteins interacting with ICP0 in Neuro-2a and 293T cells. Further experiments confirmed that SNX9 and OTUD4 restrict the replication of ICP0-null virus in neuronal cells, and OTUD4 enhances the expression of type I interferon during infection with ICP0-null virus.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Kamal L. Nahas, Viv Connor, Katharina M. Scherer, Clemens F. Kaminski, Maria Harkiolaki, Colin M. Crump, Stephen C. Graham
Summary: Herpes simplex virus-1 (HSV-1) infection causes morphological changes in cellular compartments, as well as specific organelles. These changes can be captured using soft X-ray tomography, which reveals the significant impact of HSV-1 infection on the morphology of cellular compartments.
Article
Pathology
Melissa Krystel-Whittemore, May P. Chan, Sara C. Shalin, Kenan J. Sauder, Amy Hudson, Ruth K. Foreman, Mai P. Hoang, Jeoffry B. Brennick, Shaofeng Yan, Rosalynn M. Nazarian
Summary: This study presents the first known report of herpes virus infecting deep stromal cells of the dermis, highlighting the importance of considering cutaneous stromal herpes in patients with atypical clinical lesions, especially when immunocompromised. Establishing the correct diagnosis is crucial for initiating therapy.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Review
Virology
Jun Arii
Summary: The herpes simplex virus 1 replicates its genome and transports capsids from the nucleus to the cytosol through a complex mechanism involving the nuclear egress complex. It is believed that the virus may hijack cellular machinery by using viral proteins, but the molecular mechanisms behind this phenomenon are not well understood.
Article
Virology
Carly A. I. Twigg, Alison Haugo-Crooks, Richard J. Roller
Summary: The pUL34 component of the herpes simplex virus is important for both nuclear egress and cell-to-cell spread. Mutations in pUL34 can inhibit these processes, while other mutations can improve viral replication and spread.
JOURNAL OF VIROLOGY
(2023)
Article
Dermatology
Deepthi Konda, Laxmisha Chandrashekar, Rahul Dhodapkar, Rajesh Nachiappa Ganesh, Devinder Mohan Thappa
Summary: This study characterized the clinical markers of herpes simplex virus (HSV) infection among patients with pemphigus vulgaris. It was found that male sex, presence of fissures, hemorrhagic crusts, erosions with angulated margins, linear erosions, and raised erythrocyte sedimentation rate were significantly associated with HSV infection. Hemorrhagic crusts and linear erosions were identified as independent predictors of HSV infection.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Article
Virology
Carmen Elena Gonzalez, Nawel Ben Abdeljelil, Angela Pearson
Summary: UL24 of HSV-1 plays an important role in virus infection, and its C-terminal domain regulates its nuclear and cytoplasmic localization during infection. Mutations can enhance the accumulation of UL24 in the nucleus, and specific inhibitors can block the nuclear export of UL24.
Article
Immunology
Malgorzata Krzyzowska, Anders Jarneborn, Karolina Thorn, Kristina Eriksson, Tao Jin
Summary: This study provides evidence that treatment with tofacitinib may increase the risk of disease aggravation and severe encephalitis in primary herpes simplex infection by impairing antiviral response induced by monocytes and microglia.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Susanne Pitzius, Christian Osterburg, Jakob Gebel, Georg Tascher, Birgit Schaefer, Huiqing Zhou, Christian Muench, Volker Doetsch
CELL DEATH & DISEASE
(2019)
Article
Biochemistry & Molecular Biology
Kevin Klann, Georg Tascher, Christian Muench
Article
Biochemical Research Methods
Helena C. Kenny, Georg Tascher, Anna Ziemianin, Floriane Rudwill, Alexandre Zahariev, Isabelle Chery, Guillemette Gauquelin-Koch, Marie-Pierre Barielle, Martina Heer, Stephane Blanc, Donal J. O'Gorman, Fabrice Bertile
JOURNAL OF PROTEOME RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Kevin Klann, Denisa Bojkova, Georg Tascher, Sandra Ciesek, Christian Muench, Jindrich Cinatl
Article
Multidisciplinary Sciences
Donghyuk Shin, Rukmini Mukherjee, Diana Grewe, Denisa Bojkova, Kheewoong Baek, Anshu Bhattacharya, Laura Schulz, Marek Widera, Ahmad Reza Mehdipour, Georg Tascher, Paul P. Geurink, Alexander Wilhelm, Gerbrand J. van der Heden van Noort, Huib Ovaa, Stefan Mueller, Klaus-Peter Knobeloch, Krishnaraj Rajalingam, Brenda A. Schulman, Jindrich Cinatl, Gerhard Hummer, Sandra Ciesek, Ivan Dikic
Article
Cell Biology
Nina Meyer, Lisa Henkel, Benedikt Linder, Svenja Zielke, Georg Tascher, Sandra Trautmann, Gerd Geisslinger, Christian Muench, Simone Fulda, Irmgard Tegeder, Donat Koegel
Summary: Pimozide and loperamide induce a specific form of cell death in GBM cells by triggering changes in lipid and cholesterol metabolic processes, leading to impaired lipid transport and accumulation in lysosomes. This effect is enhanced by inhibition of SMPD1 activity and results in lysosomal membrane permeabilization (LMP) and cell death. These findings suggest that targeting autophagy and lipotoxicity could be a promising approach for treating GBM.
Article
Biochemistry & Molecular Biology
Andrea Gubas, Christina Karantanou, Doris Popovic, Georg Tascher, Marina E. Hoffmann, Anna Platzek, Nina Dawe, Ivan Dikic, Daniela S. Krause, David G. McEwan
Summary: PLEKHM1 acts as an adaptor for the fusion of endocytic and autophagic vesicles with the lysosome and is regulated by mTOR and ERK2 through direct phosphorylation at a conserved region, suggesting a convergence of growth factor and amino acid-sensing pathways at PLEKHM1, placing it at a critical juncture of cellular metabolism.
Article
Biochemistry & Molecular Biology
Paul W. Hotz, Marion Wiesnet, Georg Tascher, Thomas Braun, Stefan Mueller, Luca Mendler
Article
Hematology
Christina Karantanou, Valentina R. Minciacchi, Rahul Kumar, Costanza Zanetti, Jimena Bravo, Raquel S. Pereira, Georg Tascher, Tobias Tertel, Adriana Covarrubias-Pinto, Katrin Bankov, Lisa -Marie Pfeffermann, Halvard Bonig, Paola Divieti-Pajevic, David G. McEwan, Bernd Giebel, Christian Muench, Ivan Dikic, Daniela S. Krause
Summary: Leukemia cells interact with their surrounding bone marrow microenvironment through the release of small extracellular vesicles (sEVs), promoting leukemia cell survival. However, the deficiency of PLEKHM1 in the bone marrow microenvironment accelerates BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) by affecting the cargo of sEVs released by mesenchymal stromal cells (MSCs) derived from the bone marrow. PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, leading to immature B-cell phenotype and enhanced leukemia-initiating cell (LIC) function in B-ALL. In addition, inflammatory cytokines secreted by cancer cells modulate the tumor microenvironment, further perpetuating the sEV-associated circuit.
Article
Cell Biology
Pablo Sanchez-Martin, Franziska Kriegenburg, Ludovico Alves, Julius Adam, Jana Elsaesser, Riccardo Babic, Hector Mancilla, Mariya Licheva, Georg Tascher, Christian Muench, Stefan Eimer, Claudine Kraft
Summary: Autophagy is a process in which cytosolic material is wrapped in autophagosomes and degraded in lytic compartments. The fusion of autophagosomes with lytic compartments relies on SNARE proteins, among which the conserved protein YKT6 plays a crucial role. Our study demonstrates that alterations in YKT6 function result in autophagy defects and reduced survival in both mammalian cells and nematodes.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemical Research Methods
Melinda Metzler, Rebecca George Tharyan, Kevin Klann, Katharina Grikscheit, Denisa Bojkova, Jindrich Cinatl, Georg Tascher, Sandra Ciesek, Christian Munch
Summary: The ancestral SARS-CoV-2 strain that caused the Covid-19 pandemic has evolved into multiple concerning variants with different pathogenicity and immune escape strategies. Differences in host antiviral responses to these variants remain unclear. Through whole-cell proteomics, we identified host signaling pathways that are differentially regulated upon infection with the ancestral B.1 strain and the Delta and Omicron BA.1 variants. Our findings highlight changes in the host proteome and immune responses upon infection with SARS-CoV-2 variants, providing insights into the differential pathogenicity.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Multidisciplinary Sciences
F. X. Reymond Sutandy, Ines Goessner, Georg Tascher, Christian Muench
Summary: This study demonstrates that cytosol-mitochondrial reactive oxygen species (mtROS) and accumulation of mitochondrial protein precursors in the cytosol (c-mtProt) play a critical role in initiating the mitochondrial unfolded protein response (UPRmt). The findings reveal a link between mitochondrial and cytosolic proteostasis and provide molecular insight into UPRmt signaling in human cells.
Article
Biochemistry & Molecular Biology
Rodrigo A. Gama-Brambila, Jie Chen, Jun Zhou, Georg Tascher, Christian Munich, Xinlai Cheng
Summary: PROTACs are a new technology for degrading target proteins, but limited by lack of chemical binders. By utilizing a compound O4I2 in combination with thalidomide, SF3B1 protein can be selectively degraded, inducing apoptosis and improving survival in a Drosophila intestinal tumor model.
CELL CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Rodrigo A. Gama-Brambila, Jie Chen, Yasamin Dabiri, Georg Tascher, Vaclav Nemec, Christian Muench, Guangqi Song, Stefan Knapp, Xinlai Cheng
Summary: The discovery of clustered regularly interspaced short palindromic repeats and their associated proteins has led to the development of new methods to control Cas proteins, including fusion proteins and PROTACs. Engineering Cas proteins with a pi-clamp system allows for labeling and degradation in live cells, showing a wide range of potential applications in regulating stability and activity of FCPF-tagging proteins through perfluoroaromatics-induced proximity.
Article
Cell Biology
Christof Hiebel, Elisabeth Sturner, Meike Hoffmeister, Georg Tascher, Mario Schwarz, Heike Nagel, Christian Behrends, Christian Munch, Christian Behl