Why large icosahedral viruses need scaffolding proteins

While small single-stranded viral shells encapsidate their genome spontaneously, many large viruses, such as the herpes simplex virus or infectious bursal disease virus (IBDV), typically require a template, consisting of either scaffolding proteins or an inner core. Despite the proliferation of large viruses in nature, the mechanisms by which hundreds or thousands of proteins assemble to form structures with icosahedral order (IO) is completely unknown. Using continuum elasticity theory, we study the growth of large viral shells (capsids) and show that a nonspecific template not only selects the radius of the capsid, but also leads to the error-free assembly of protein subunits into capsids with universal IO. We prove that as a spherical cap grows, there is a deep potential well at the locations of disclinations that later in the assembly process will become the vertices of an icosahedron. Furthermore, we introduce a minimal model and simulate the assembly of a viral shell around a template under nonequilibrium conditions and find a perfect match between the results of continuum elasticity theory and the numerical simulations. Besides explaining available experimental results, we provide a number of predictions. Implications for other problems in spherical crystals are also discussed.