SNAP output for PDB entry 7ozr [SNAP web server]

PDB-id

7ozr; SNAP-derived features in text and JSON formats; DNAproDB

Class

virus

Method

cryo-EM (4.5 Å)

Summary

Subtomogram average of authentic mumps virus nucleocapsid from hela cell lysate of long helical pitch

Reference

Zhang X, Sridharan S, Zagoriy I, Eugster Oegema C, Ching C, Pflaesterer T, Fung HKH, Becher I, Poser I, Muller CW, Hyman AA, Savitski MM, Mahamid J (2023): "Molecular mechanisms of stress-induced reactivation in mumps virus condensates." Cell, 186, 1877-1894.e27. doi: 10.1016/j.cell.2023.03.015.

Abstract

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.