Article
Microbiology
Johannes Schweininger, Myriam Scherer, Franziska Rothemund, Eva-Maria Schilling, Sonja Worz, Thomas Stamminger, Yves A. Muller
Summary: Cytomegaloviruses have evolved a species-specific IE1 protein tertiary structure to effectively bind and inactivate the important cellular restriction factor PML, forming a barrier to cross-species transmission. The highly conserved fold of IE1 maximizes the efficacy of PML targeting in a species-specific manner, illustrating the co-evolution of viruses and their hosts.
Review
Virology
Boris Ryabchenko, Vojtech Sroller, Lenka Hornikova, Alexey Lovtsov, Jitka Forstova, Sandra Huerfano
Summary: This review provides detailed descriptions of the diverse and complex interactions between small and medium size DNA viruses and promyelocytic leukemia nuclear bodies (PM NBs). The interactions between PM NB components and viruses can influence viral genome expression and/or replication, as well as IFN-mediated or apoptotic cell responses to viral infection. The review also discusses the interactions between PM NBs and Hepatitis B virus, papillomaviruses, polyomaviruses, and avian anellovirus. Despite numerous studies on the functions of PM NBs in the context of viral infection, there are still gaps in our understanding of the fine interactions between viruses and the highly dynamic PM NBs, which require further investigation.
Article
Biology
Myriam Scherer, Clarissa Read, Gregor Neusser, Christine Kranz, Anna K. Kuderna, Regina Mueller, Florian Full, Sonja Woerz, Anna Reichel, Eva-Maria Schilling, Paul Walther, Thomas Stamminger
Summary: PML nuclear bodies undergo rearrangement to form giant cages upon viral infection, trapping viral genomes and capsids, and providing a multilayered defense strategy against viral infections.
Article
Multidisciplinary Sciences
Seishiro Hirano, Osamu Udagawa
Summary: Promyelocytic leukemia (PML) proteins play a role in the development of acute promyelocytic leukemia (APL) and can be affected by trivalent arsenic (As3+). The exposure to As3+ can lead to changes in PML-NBs, including solubility shift, SUMOylation, and late agglomeration. Understanding these changes is important for the regulation of intranuclear dynamics of PML-NBs.
Article
Biochemistry & Molecular Biology
Sven Seitz, Anna Theresa Heusel, Thomas Stamminger, Myriam Scherer
Summary: PML nuclear bodies (PML-NBs) play a cell type-specific antiviral role against HCMV infection, with PML and Daxx having contrasting effects at different stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Isabella Fraschilla, Hajera Amatullah, Raza-Ur Rahman, Kate L. Jeffrey
Summary: Inflammatory bowel disease (IBD) is a disease influenced by both genetic and environmental factors, including commensal microorganisms. This study identifies a role for Speckled Protein 140 (SP140) in regulating immune responses to prevent the expansion of inflammatory bacteria. It is found that deficiency of SP140 leads to severe colitis in mice, which can be transmitted and improved with antibiotics. Additionally, SP140 deficiency results in an overgrowth of certain bacteria in both mice and humans. Patients with SP140 deficiency and mice lacking SP140 also exhibit altered antimicrobial defense mechanisms. Therefore, mutations within the SP140 gene may contribute to the development of human diseases associated with microbiota.
CELL HOST & MICROBE
(2022)
Review
Virology
Eva-Maria Schilling, Myriam Scherer, Thomas Stamminger
Summary: Cellular restriction factors act as important innate immune barriers against viruses, including HCMV. Multiple RFs have been identified to counteract HCMV infection, affecting different steps of the viral replication cycle. Understanding the interplay between host RFs and viral antagonists is essential for developing new approaches to combat HCMV infection.
Article
Biochemistry & Molecular Biology
Liyang Wu, Ting Pan, Mo Zhou, Tao Chen, Shiyu Wu, Xi Lv, Jun Liu, Fei Yu, Yuanjun Guan, Bingfeng Liu, Wanying Zhang, Xiaohui Deng, Qianyu Chen, Anqi Liang, Yingtong Lin, Lilin Wang, Xiaoping Tang, Weiping Cai, Linghua Li, Xin He, Hui Zhang, Xiancai Ma
Summary: CBX4 has been identified as a key factor in HIV-1 latency, acting as a bridge between the repressor complexes PRC1 and PRC2 to maintain viral latency. This discovery sheds light on potential interventions for reactivating latent HIV-1 infection.
Article
Virology
Franziska Rothemund, Myriam Scherer, Eva-Maria Schilling, Johannes Schweininger, Yves A. Muller, Thomas Stamminger
Summary: The study analyzed the functions of human cytomegalovirus (CMV) immediate early 1 (IE1) protein and rat CMV IE1 (rIE1) protein, and found that their interactions with cellular proteins PML and FEN1 were species-specific. It was also discovered that both IE1 proteins can antagonize human STAT2, but different regions of the viral proteins were involved in the interaction. Additionally, the study revealed that the binding of PML, FEN1, and STAT2 was conserved between primate and rodent proteins, but rIE1 lacked chromatin tethering function.
Article
Multidisciplinary Sciences
Orhi Barroso-Gomila, Fredrik Trulsson, Veronica Muratore, Inigo Canosa, Laura Merino-Cacho, Ana Rosa Cortazar, Coralia Perez, Mikel Azkargorta, Ibon Iloro, Arkaitz Carracedo, Ana M. Aransay, Felix Elortza, Ugo Mayor, Alfred C. O. Vertegaal, Rosa Barrio, James D. Sutherland
Summary: SUMO-ID technology combines TurboID proximity biotinylation and protein-fragment complementation to study SUMO-dependent interactions, providing insight into the complexity of the ubiquitin code.
NATURE COMMUNICATIONS
(2021)
Review
Virology
Behdokht Jan Fada, Eleazar Reward, Haidong Gu
Summary: ND10, also known as PML-NBs, are dynamic membraneless subnuclear domains involved in key cellular processes such as DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses.
Article
Microbiology
Tejaswini S. Reddi, Philipp E. Merkl, So-Yon Lim, Norman L. Letvin, David M. Knipe
Summary: TRIM22 is a novel restriction factor that can combat DNA viruses, particularly HSV-1, and is not degraded by viral ICP0 protein. It also inhibits other types of herpesviruses and different genetic variants of TRIM22 show varying levels of effectiveness against HSV-1.
Review
Biochemistry & Molecular Biology
Martina Ugge, Matilde Simoni, Cristina Fracassi, Rosa Bernardi
Summary: This review explores the contribution of PML splicing isoforms to the activities of PML-NBs, revealing the differences in formation and function of these isoforms. It suggests that future research should delve into the contribution of isoform specificity to help elucidate the complex functionality of the PML gene.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Weronika Karle, Samuel Becker, Philipp Stenzel, Christoph Knosalla, Guenter Siegel, Oliver Baum, Andreas Zakrzewicz, Janine Berkholz
Summary: The study found that PML is strongly expressed in atherosclerotic coronary arteries and concentrated in smooth muscle cells in plaque areas. Transfection of cells with intact PML gene resulted in higher levels of SUMOylated proteins but lower differentiation markers, leading to increased proliferation and migration activities. PML was upregulated only after IFN-gamma stimulation, indicating its role in the molecular cascades associated with atherosclerosis pathogenesis.
Review
Veterinary Sciences
Sabari Nath Neerukonda
Summary: PML NBs are nuclear membrane-less sub structures that play critical roles in various cellular pathways, including antiviral immunity. They have substantial roles not only in DNA viruses but also in RNA viruses. Viruses reorganize PML NBs to create a cellular environment favorable for replication and pathogenesis.
VETERINARY SCIENCES
(2021)
Article
Microbiology
Florian Full, Michiel van Gent, Konstantin M. J. Sparrer, Cindy Chiang, Matthew A. Zurenski, Myriam Scherer, Norbert H. Brockmeyer, Lucie Heinzerling, Michael Sturzl, Klaus Korn, Thomas Stamminger, Armin Ensser, Michaela U. Gack
NATURE MICROBIOLOGY
(2019)
Review
Virology
Manfred Marschall, Sigrun Haege, Marcus Conrad, Sewar Alkhashrom, Jintawee Kicuntod, Johannes Schweininger, Mark Kriegel, Josephine Loesing, Julia Tillmanns, Frank Neipel, Jutta Eichler, Yves A. Muller, Heinrich Sticht
Article
Microbiology
Meta Volcic, Konstantin M. J. Sparrer, Lennart Koepke, Dominik Hotter, Daniel Sauter, Christina M. Stuerzel, Myriam Scherer, Thomas Stamminger, Thomas G. Hofmann, Nathalie J. Arhel, Lisa Wiesmueller, Frank Kirchhoff
NATURE MICROBIOLOGY
(2020)
Review
Virology
Eva-Maria Schilling, Myriam Scherer, Thomas Stamminger
Summary: Cellular restriction factors act as important innate immune barriers against viruses, including HCMV. Multiple RFs have been identified to counteract HCMV infection, affecting different steps of the viral replication cycle. Understanding the interplay between host RFs and viral antagonists is essential for developing new approaches to combat HCMV infection.
Article
Virology
Sewar Alkhashrom, Jintawee Kicuntod, Sigrun Haege, Johannes Schweininger, Yves A. Muller, Peter Lischka, Manfred Marschall, Jutta Eichler
Summary: The study identified a new type of small molecule inhibitors that can inhibit HCMV core NEC formation and have antiviral effects on HCMV infection.
Article
Microbiology
Eva-Maria Schilling, Myriam Scherer, Franziska Rothemund, Thomas Stamminger
Summary: FEN1 plays a critical role in viral infections, especially in HCMV infection where IE1 can manipulate FEN1 to facilitate viral DNA replication. This discovery may lead to new antiviral therapeutic options to combat HCMV infections.
Article
Microbiology
Johannes Schweininger, Myriam Scherer, Franziska Rothemund, Eva-Maria Schilling, Sonja Worz, Thomas Stamminger, Yves A. Muller
Summary: Cytomegaloviruses have evolved a species-specific IE1 protein tertiary structure to effectively bind and inactivate the important cellular restriction factor PML, forming a barrier to cross-species transmission. The highly conserved fold of IE1 maximizes the efficacy of PML targeting in a species-specific manner, illustrating the co-evolution of viruses and their hosts.
Article
Biochemistry & Molecular Biology
Johannes Schweininger, Mark Kriegel, Sigrun Hage, Marcus Conrad, Sewar Alkhashrom, Josephine Losing, Sigrid Weiler, Julia Tillmanns, Claudia Egerer-Sieber, Andrea Decker, Tihana Lenac Rovis, Jutta Eichler, Heinrich Sticht, Manfred Marschall, Yves A. Muller
Summary: The formation of the core nuclear egress complex (NEC) in varicella-zoster virus (VZV) displays subfamily-specific features. Understanding these features is crucial for developing drugs that target multiple herpesviruses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Myriam Scherer, Clarissa Read, Gregor Neusser, Christine Kranz, Anna K. Kuderna, Regina Mueller, Florian Full, Sonja Woerz, Anna Reichel, Eva-Maria Schilling, Paul Walther, Thomas Stamminger
Summary: PML nuclear bodies undergo rearrangement to form giant cages upon viral infection, trapping viral genomes and capsids, and providing a multilayered defense strategy against viral infections.
Article
Virology
Franziska Rothemund, Myriam Scherer, Eva-Maria Schilling, Johannes Schweininger, Yves A. Muller, Thomas Stamminger
Summary: The study analyzed the functions of human cytomegalovirus (CMV) immediate early 1 (IE1) protein and rat CMV IE1 (rIE1) protein, and found that their interactions with cellular proteins PML and FEN1 were species-specific. It was also discovered that both IE1 proteins can antagonize human STAT2, but different regions of the viral proteins were involved in the interaction. Additionally, the study revealed that the binding of PML, FEN1, and STAT2 was conserved between primate and rodent proteins, but rIE1 lacked chromatin tethering function.
Article
Microbiology
Anne-Charlotte Stilp, Myriam Scherer, Patrick Koenig, Axel Fuerstberger, Hans A. Kestler, Thomas Stamminger
Summary: In this study, it was discovered that the chromatin remodeling factor ATRX has a co-activating role in innate immunity, regulating chromatin accessibility and transcription of interferons and interferon-stimulated genes. It affects the antiviral immune response by decreasing transcription and secretion of type I interferons, leading to reduced expression of interferon-stimulated genes.
Article
Biochemistry & Molecular Biology
Martin Schuetz, Regina Mueller, Eileen Socher, Christina Wangen, Florian Full, Emanuel Wyler, Diana Wong, Myriam Scherer, Thomas Stamminger, Sunwen Chou, William D. Rawlinson, Stuart T. Hamilton, Heinrich Sticht, Manfred Marschall
Summary: The complex host interaction network of human cytomegalovirus (HCMV) involves the regulatory protein kinase pUL97 and human cyclins. The study found that cyclin H is a crucial determinant of pUL97 kinase activity and viral replication efficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sven Seitz, Anna Theresa Heusel, Thomas Stamminger, Myriam Scherer
Summary: PML nuclear bodies (PML-NBs) play a cell type-specific antiviral role against HCMV infection, with PML and Daxx having contrasting effects at different stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)