The different faces of mass action in virus assembly.

The spontaneous encapsulation of genomic and non-genomic polyanions by coat proteins of simple icosahedral viruses is driven, in the first instance, by electrostatic interactions with polycationic RNA binding domains on these proteins. The efficiency with which the polyanions can be encapsulated in vitro, and presumably also in vivo, must in addition be governed by the loss of translational and mixing entropy associated with co-assembly, at least if this co-assembly constitutes a reversible process. These forms of entropy counteract the impact of attractive interactions between the constituents and hence they counteract complexation. By invoking mass action-type arguments and a simple model describing electrostatic interactions, we show how these forms of entropy might settle the competition between negatively charged polymers of different molecular weights for co-assembly with the coat proteins. In direct competition, mass action turns out to strongly work against the encapsulation of RNAs that are significantly shorter, which is typically the case for non-viral (host) RNAs. We also find that coat proteins favor forming virus particles over nonspecific binding to other proteins in the cytosol even if these are present in vast excess. Our results rationalize a number of recent in vitro co-assembly experiments showing that short polyanions are less effective at attracting virus coat proteins to form virus-like particles than long ones do, even if both are present at equal weight concentrations in the assembly mixture.