Initial condition for simulation. The initial condition for our simulation is set by a fixed number of infectious extracellular virus particles per cell (V ex (0)). At time zero (t ¼ 0), the number of bound virus particles and the level of all viral components within cells are zero. In our model, binding of extracellular virus particles to cells reduces their level (Equation 1), and an encapsidated genome and stoichiometric amounts of viral proteins (Table 2 , [28, 29] ) are then immediately released from each bound virus particle to the cytoplasm. Specifically, we assume that all N proteins from a bound virus particle are released as a form of encapsidated genome complex. Downstream processes, beginning with transcription, are then initiated. In our simulation, viral infection starts with rib_host ¼ 0.99 (with rib_host ¼ 0.9, ; 0.9995 simulations showed the same results). Other key model parameters for simulation are summarized in Table 1 . In addition, a nomenclature list is shown in Table 4 . Figure S1 . Ratio of Genome to Anti-Genome During Simulated VSV Infection Depends on Relative Promoter Strengths The relative strength of the anti-genomic promoter relative to the genomic promoter is given by S prom . PI stands for time post-infection. Figure S4 . Productivity Ranking of Six Gene-Shuffled Viruses Provides Parameter Constraint For each value of S cond and its corresponding host parameter values (k d,host and S rib ), the virus productivity of each gene-shuffled virus in BHK cells was determined and normalized by the highest productivity. Simulated rankings of six strains matched experimentally observed rankings [9] over a narrow range of S cond , indicated by the bar. Initial number of infectious extracellular virus particles per cell was three. Found at DOI: 10.1371/journal.pcbi/0020116.sg004 (872 KB TIF).