Published in Cell, 2023
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.
Recommended citation: Zhang, X., Sridharan, S., Zagoriy, I., Eugster Oegema, C., Ching, C., Pflaesterer, T., Fung, H. K. H., Becher, I., Poser, I., Müller, C. W., Hyman, A. A., Savitski, M. M., & Mahamid, J. (2023). Molecular mechanisms of stress-induced reactivation in mumps virus condensates. Cell, 186(9), 1877-1894.e27. https://www.sciencedirect.com/science/article/pii/S0092867423002763
