Molecular mechanisms of stress-induced reactivation in mumps virus condensates

Cell. 2023 Apr 27;186(9):1877-1894.e27. doi: 10.1016/j.cell.2023.03.015.


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.

Keywords: IDR; biomolecular condensates; cryo-electron tomography; cryo-focused ion beam; in-cell structural biology; intrinsically disordered regions; nucleocapsid; persistent infection; phosphorylation; viral replication; whole-cell proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Mumps virus* / physiology
  • Nucleocapsid
  • Persistent Infection*
  • Phosphoproteins / metabolism
  • Virus Replication


  • Phosphoproteins