Building a viral capsid in the presence of genomic RNA

Virus capsid assembly has traditionally been considered as a process that can be described primarily via self-assembly of the capsid proteins, neglecting interactions with other viral or cellular components. Our recent work on several ssRNA viruses, a major class of viral pathogens containing important human, animal, and plant viruses, has shown that this protein-centric view is too simplistic. Capsid assembly for these viruses relies strongly on a number of cooperative roles played by the genomic RNA. This realization requires a new theoretical framework for the modeling and prediction of the assembly behavior of these viruses. In a seminal paper Zlotnick [J. Mol. Biol. 241, 59 (1994)] laid the foundations for the modeling of capsid assembly as a protein-only self-assembly process, illustrating his approach using the example of a dodecahedral study system. We describe here a generalized framework for modeling assembly that incorporates the regulatory functions provided by cognate protein-nucleic-acid interactions between capsid proteins and segments of the genomic RNA, called packaging signals, into the model. Using the same dodecahedron system we demonstrate, using a Gillespie-type algorithm to deal with the enhanced complexity of the problem instead of a master equation approach, that assembly kinetics and yield strongly depend on the distribution and nature of the packaging signals, highlighting the importance of the crucial roles of the RNA in this process.