To Build a Virus on a Nucleic Acid Substrate

Many viruses package their genomes concomitant with assembly. Here, we show that this reaction can be described by three coefficients: association of capsid protein (CP) to nucleic acid (NA), K-NA; CP-CP interaction, omega; and alpha, proportional to the work required to package NA. The value of alpha can vary as NA is packaged. A phase diagram of average In alpha versus In omega identifies conditions where assembly is likely to fail or succeed. NA morphology can favor (In alpha > 0) or impede (In alpha < 0) assembly. As In omega becomes larger, capsids become more stable and assembly becomes more cooperative. Where (In alpha + In omega) < 0, the CP is unable to contain the NA, so that assembly results in aberrant particles. This phase diagram is consistent with quantitative studies of cowpea chlorotic mottle virus, hepatitis B virus, and simian virus 40 assembling on ssRNA and dsDNA substrates. Thus, the formalism we develop is suitable for describing and predicting behavior of experimental studies of CP assembly on NA.