Effects of relative promoter strength on viral growth. The genome and anti-genome of VSV are synthesized in unequal amounts, determined by the differing strengths of their promoters [19, 31, 33, 39] . The stronger promoter of the antigenome allows viral polymerases to produce more genomes to meet their demands as components of virion particles and as templates for transcription and replication. To explore how VSV growth is influenced by differences in the relative strength of the genomic and anti-genomic promoters, we predicted the yield of virus on BHK and DBT cells over a broad range of S prom , as shown in Figure 6A . Small S prom virus cannot grow well because most polymerases would be associated with genomes and tend to synthesize primarily anti-genomes. For example, for S prom equal to 0.1, infected BHK and DBT cells make 5-fold and 26-fold fewer progeny than wild-type VSV infected cells, respectively. However, large S prom virus also cannot grow well because most polymerases would preferentially bind to newly synthesized anti-genomes, producing few of the anti-genomes that are needed as templates to amplify genomes. Our simulations predicted that values of 30 and 50 for S prom would be optimal for VSV growth in BHK and DBT cells, respectively ( Figure 6A ). The estimated wild-type value of S prom of 5.4 gives VSV yields higher than 80% of their maximum yields for both cell types ( Figure 6A) .