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TitleMolecular mechanisms of stress-induced reactivation in mumps virus condensates.
Journal, issue, pagesCell, Vol. 186, Issue 9, Page 1877-1894.e27, Year 2023
Publish dateApr 27, 2023
AuthorsXiaojie 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 AbstractNegative-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.
External linksCell / PubMed:37116470 / PubMed Central
MethodsEM (subtomogram averaging) / EM (tomography)
Resolution4.5 - 6.5 Å
Structure data

13133

7ozr

EMDB-13133, PDB-7ozr:
Subtomogram average of authentic mumps virus nucleocapsid from HeLa cell lysate of long helical pitch
Method: EM (subtomogram averaging) / Resolution: 4.5 Å

EMDB-13136: Subtomogram average of authentic mumps virus nucleocapsid from HeLa cell lysate of short helical pitch
Method: EM (subtomogram averaging) / Resolution: 6.3 Å

EMDB-13137: In-cell subtomogram average of authentic mumps virus nucleocapsid in HeLa cells
Method: EM (subtomogram averaging) / Resolution: 6.5 Å

EMDB-13165: Mumps viral factory in a non-stressed HeLa cell in a chronic infection stage
Method: EM (tomography)

EMDB-13166: Mumps viral factory at a chronic infection stage in a HeLa cell under acute arsenite stress
Method: EM (tomography)

EMDB-13167: Mumps viral factory at a chronic infection stage in a HeLa cell under prolonged mild arsenite stress
Method: EM (tomography)

Source
  • mumps virus genotype a
KeywordsVIRUS / Helical filament / Nucleocapsid / Protein-RNA complex / Scaffold

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