Molecular mechanism of stress-induced reactivation in mumps virus condensates

Abstract

Negative-stranded RNA viruses can establish both acute and chronic infections, and some have developed the ability to switch between the two. However, the molecular mechanisms that trigger reactivation of viral replication from chronic infection and link to pathogenesis remain largely unknown. Here, we investigated the role of cellular stress in provoking a chronic-to-acute-like transition of viral replication in a model of mumps infection. Using whole-cell proteomics, cell biology, cryo-electron tomography and subtomogram averaging, we show that stress induces an increase in phosphorylation of the disordered viral phosphoprotein, and the propensity of the viral polymerase to partition into preformed condensates termed replication factories.