Should virus capsids assemble perfectly? Theory and observation of defects

Abstract

Although published structural models of viral capsids generally exhibit a high degree of regularity or symmetry, structural defects might be expected because of the fluctuating environment in which capsids assemble and the requirement of some capsids for disassembly prior to genome delivery. Defective structures are observed in computer simulations, and are evident in single-particle cryoEM studies. Here, we quantify the conditions under which defects might be expected, using a statistical mechanics model allowing for ideal, defective, and vacant sites. The model displays a threshold in affinity parameters below which there is an appreciable population of defective capsids. Even when defective sites are not allowed, there is generally some population of vacancies. Analysis of single particles in cryoEM micrographs yields a confirmatory {gtrsim}15% of defective particles. Our findings suggest structural heterogeneity in virus capsids may be under-appreciated, and also points to a non-traditional strategy for assembly inhibition.