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-Structure paper
タイトル | Molecular mechanisms of stress-induced reactivation in mumps virus condensates. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 9, Page 1877-1894.e27, Year 2023 |
掲載日 | 2023年4月27日 |
著者 | Xiaojie Zhang / Sindhuja Sridharan / Ievgeniia Zagoriy / Christina Eugster Oegema / Cyan Ching / Tim Pflaesterer / Herman K H Fung / Isabelle Becher / Ina Poser / Christoph W Müller / Anthony A Hyman / Mikhail M Savitski / Julia Mahamid / |
PubMed 要旨 | Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular ...Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular stress disrupts the metastable host-virus equilibrium in persistent infection and induces viral replication in a culture model of mumps virus. Using a combination of cell biology, whole-cell proteomics, and cryo-electron tomography, we show that persistent viral replication factories are dynamic condensates and identify the largely disordered viral phosphoprotein as a driver of their assembly. Upon stress, increased phosphorylation of the phosphoprotein at its interaction interface with the viral polymerase coincides with the formation of a stable replication complex. By obtaining atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events constitute a stress-mediated switch within viral condensates that provide an environment to support upregulation of viral replication. |
リンク | Cell / PubMed:37116470 / PubMed Central |
手法 | EM (サブトモグラム平均) / EM (トモグラフィー) |
解像度 | 4.5 - 6.5 Å |
構造データ | EMDB-13133, PDB-7ozr: EMDB-13136: Subtomogram average of authentic mumps virus nucleocapsid from HeLa cell lysate of short helical pitch EMDB-13137: In-cell subtomogram average of authentic mumps virus nucleocapsid in HeLa cells EMDB-13165: Mumps viral factory in a non-stressed HeLa cell in a chronic infection stage EMDB-13166: Mumps viral factory at a chronic infection stage in a HeLa cell under acute arsenite stress EMDB-13167: Mumps viral factory at a chronic infection stage in a HeLa cell under prolonged mild arsenite stress |
由来 |
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キーワード | VIRUS / Helical filament / Nucleocapsid / Protein-RNA complex / Scaffold |