The thermodynamics of virus capsid assembly.

Virus capsid assembly is a critical step in the viral life cycle. The underlying basis of capsid stability is key to understanding this process. Capsid subunits interact with weak individual contact energies to form a globally stable icosahedral lattice; this structure is ideal for encapsidating the viral genome and host partners and protecting its contents upon secretion, yet the unique properties of its assembly and inter-subunit contacts allow the capsid to dissociate upon entering a new host cell. The stability of the capsid can be analyzed by treating capsid assembly as an equilibrium polymerization reaction, modified from the traditional polymer model to account for the fact that a separate nucleus is formed for each individual capsid. From the concentrations of reactants and products in an equilibrated assembly reaction, it is possible to extract the thermodynamic parameters of assembly for a wide array of icosahedral viruses using well-characterized biochemical and biophysical methods. In this chapter we describe this basic analysis and provide examples of thermodynamic assembly data for several different icosahedral viruses. These data provide new insights into the assembly mechanisms of spherical virus capsids, as well as into the biology of the viral life cycle.