ジャーナル: Cell / 年: 2023 タイトル: Molecular mechanisms of stress-induced reactivation in mumps virus condensates. 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 / ...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 / 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.