Watching Measles virus factories at work in liquid droplets

Many viruses are known to form cellular compartments, also called viral factories. Paramyxoviruses, including measles virus, colocalize their proteomic and genomic material in puncta in infected cells. Researchers from FDP, VRM and IRPAS groups at IBS demonstrate that purified nucleo- (N) and phospho- (P) proteins of Measles virus form liquid-like membraneless organelles upon mixing in vitro. They identify weak interactions involving intrinsically disordered domains of N and P that are implicated in this process, one of which is essential for phase separation. Fluorescence allows them to follow the modulation of the dynamics of N and P upon droplet formation while NMR is used to investigate the thermodynamics of this process. RNA colocalizes to droplets, where it triggers assembly of N protomers into nucleocapsid-like particles that encapsidate the RNA. The rate of encapsidation within droplets is enhanced compared to the dilute phase, revealing one of the roles of liquid-liquid phase separation in Measles virus replication. This study allows us to observe viral factories in action for the first time. The presence of similar puncta in numerous negative sense RNA viruses suggests that the observations made here will be of general interest in the development of antiviral strategies.

Measles Virus Nucleo- and Phosphoproteins form Liquid-like Phase-Separated Compartments that Promote Nucleocapsid Assembly. Serafima Guseva Sigrid Milles, Malene Ringkjøbing Jensen, Nicola Salvi, Jean-Phillipe Kleman, Damien Maurin, Rob W.H. Ruigrok, Martin Blackledge. Science Advances ; Vol. 6, no. 14, eaaz7095