  Previous self-assembly experiments on a model icosahedral plant virus have
shown that, under physiological conditions, capsid proteins initially bind to
the genome through an en masse mechanism and form nucleoprotein complexes in a
disordered state, which raises the questions as to how virions are assembled
into a highly ordered structure in the host cell. Using small-angle X-ray
scattering, we find out that a disorder-order transition occurs under
physiological conditions upon an increase in capsid protein concentrations. Our
cryo-transmission electron microscopy reveals closed spherical shells
containing in vitro transcribed viral RNA even at pH 7.5, in marked contrast
with the previous observations. We use Monte Carlo simulations to explain this
disorder-order transition and find that, as the shell grows, the structures of
disordered intermediates in which the distribution of pentamers does not belong
to the icosahedral subgroups become energetically so unfavorable that the caps
can easily dissociate and reassemble overcoming the energy barriers for the
formation of perfect icosahedral shells. In addition, we monitor the growth of
capsids under the condition that the nucleation and growth is the dominant
pathway and show that the key for the disorder-order transition in both en
masse and nucleation and growth pathways lies in the strength of elastic energy
compared to the other forces in the system including protein-protein
interactions and the chemical potential of free subunits. Our findings explain,
at least in part, why perfect virions with icosahedral order form under
different conditions including physiological ones.
