A virus
in its most simple form is comprised of a protein capsid
that surrounds and protects the viral genome. The self-assembly of
such structures, however, is a highly complex, multiprotein, multiinteraction
process and has been a topic of study for a number of years. This
self-assembly process is driven by the (mainly electrostatic) interaction
between the capsid proteins (CPs) and the genome as well as by the
protein–protein interactions, which primarily rely on hydrophobic
interactions. Insight in the thermodynamics that is involved in virus
and virus-like particle (VLP) formation is crucial in the detailed
understanding of this complex assembly process. Therefore, we studied
the assembly of CPs of the cowpea chlorotic mottle virus (CCMV) templated
by polyanionic species (cargo), that is, single-stranded DNA (ssDNA),
and polystyrene sulfonate (PSS) using isothermal titration calorimetry.
By separating the electrostatic CP–cargo interaction from the
full assembly interaction, we conclude that CP–CP interactions
cause an enthalpy change of −3 to −4 kcal mol–1 CP. Furthermore, we quantify that upon reducing the CP–CP
interaction, in the case of CCMV by increasing the pH to 7, the CP–cargo
starts to dominate VLP formation. This is highlighted by the three
times higher affinity between CP and PSS compared to CP and ssDNA,
resulting in the disassembly of CCMV at neutral pH in the presence
of PSS to yield PSS-filled VLPs.