Effect of Ionic Strength on the Assembly of Simian Vacuolating Virus Capsid Protein Around Poly(Styrene Sulfonate)

Virus-like particles (VLPs) are noninfectious nanocapsules that can be used for drug delivery or vaccine applications. VLPs can be assembled from virus capsid proteins around a condensing agent like RNA, DNA, or a charged polymer. Electrostatic interactions play an important role in the assembly reaction. VLPs assemble from many copies of capsid protein, with combinatorial intermediates, and therefore the mechanism of the reaction is poorly understood. In this paper, we determined the effect of ionic strength on the assembly of Simian Vacuolating Virus 40 (SV40)-like particles. We mixed poly(styrene sulfonate) with SV40 capsid protein pentamers at different ionic strengths. We then characterized the assembly product by solution small-angle X-ray scattering (SAXS) and cryo-TEM. To analyze the data, we performed Brownian dynamics simulations using a coarse-grained model that revealed incomplete, asymmetric VLP structures that were consistent with the experimental data. We found that close to physiological ionic strength, T=1 VLPs coexisted with VP1 pentamers. At lower or higher ionic strengths, incomplete particles coexisted with pentamers and T=1 particles. Including the simulation, structures were essential to explaining the SAXS data.