NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice
| Autor: | Susann Kummer, Hans-Georg Kräusslich, Psylvia Léger, Steeve Boulant, Jana Koch, Pierre-Yves Lozach, Megan L. Stanifer, Qilin Xin, Michèle Bouloy, Robin Burk, Carmen Nussbaum-Krammer, Carole Tamietti, Marie Flamand, Karsten Richter, Eliana Nachman, Xavier Montagutelli |
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| Přispěvatelé: | Heidelberg University Hospital [Heidelberg], Center for Molecular Biology - Zentrum für Molekulare Biologie [Heidelberg, Germany] (ZMBH), Universität Heidelberg [Heidelberg] = Heidelberg University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Moléculaire des Bunyavirus, Institut Pasteur [Paris] (IP), Génétique de la souris - Mouse Genetics, This work was supported by grants from CellNetworks Research Group funds, Heidelberg, and from the Deutsche Forschungsgemeinschaft (DFG, LO-2338/1-1 and LO-2338/3-1). It was also supported by a Chinese Scholarship Council fellowship to Q.X, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Rift Valley Fever General Physics and Astronomy Protein aggregation Viral Nonstructural Proteins MESH: Virulence Virulence factor chemistry.chemical_compound Mice MESH: Chlorocebus aethiops Chlorocebus aethiops MESH: Rift Valley Fever MESH: Microscopy Confocal MESH: Animals lcsh:Science Multidisciplinary Microscopy Confocal MESH: Protein Aggregation Pathological Virulence Virus structures 3. Good health [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Microscopy Electron Transmission MESH: Rift Valley fever virus Thioflavin Encephalitis MESH: Cell Nucleus Amyloid MESH: Cell Line Tumor Virulence Factors Prions Science MESH: Vero Cells Amyloidogenic Proteins macromolecular substances Biology Fibril Protein Aggregation Pathological General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Microscopy Electron Transmission Cell Line Tumor mental disorders medicine Animals Humans Vero Cells MESH: Mice MESH: Virulence Factors Cell Nucleus MESH: Amyloid MESH: Amyloidogenic Proteins MESH: Humans 030102 biochemistry & molecular biology General Chemistry medicine.disease Rift Valley fever virus Virology 030104 developmental biology chemistry MESH: HeLa Cells Vero cell MESH: Viral Nonstructural Proteins lcsh:Q HeLa Cells |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-19 (2020) Nature Communications Nature Communications, 2020, 11 (1), pp.3281. ⟨10.1038/s41467-020-17101-y⟩ Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.3281. ⟨10.1038/s41467-020-17101-y⟩ |
| ISSN: | 2041-1723 |
| Popis: | Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer’s disease. Here we show that the major virulence factor of Rift Valley fever virus, the protein NSs, forms filamentous structures in the brain of mice and affects mortality. NSs assembles into nuclear and cytosolic disulfide bond-dependent fibrillary aggregates in infected cells. NSs structural arrangements exhibit characteristics typical for amyloids, such as an ultrastructure of 12 nm-width fibrils, a strong detergent resistance, and interactions with the amyloid-binding dye Thioflavin-S. The assembly dynamics of viral amyloid-like fibrils can be visualized in real-time. They form spontaneously and grow in an amyloid fashion within 5 hours. Together, our results demonstrate that viruses can encode amyloid-like fibril-forming proteins and have strong implications for future research on amyloid aggregation and toxicity in general. Rift Valley fever virus (RVFV) can cause severe diseases in humans, including encephalitis. Here the authors show that NSs, the major virulence factor of RVFV, is an amyloidogenic protein forming fibrils in infected mouse brains and causing increased mortality in mice. |
| Databáze: | OpenAIRE |
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