How does a simple virus self-assemble?*

Simple RNA viruses consist of proteins that form a highly-ordered protective shell (called a capsid) around the viral RNA. Many such viruses are self-assembled: infectious viral particles form spontaneously in a mixture of RNA and coat protein. The yield and fidelity of the assembly is particularly remarkable in viruses with a triangulation number of 3 or higher, in which case some of the proteins must find their way to 5-fold-symmetry sites and others to 3-fold sites in the same shell. To understand how such systems assemble, we use interferometric techniques to measure the scattering of a single assembling viral particle (MS2 bacteriophage) as a function of time. By comparing the scattered intensity to that of the wild-type virus, we infer the mass of proteins that have attached to the central RNA on time scales ranging from milliseconds to minutes. We find that individual particles grow to nearly full size in a short time following a much longer delay period. The distribution of delay times suggests that the assembly follows a nucleation-and-growth pathway.