How can a detailed model for the intracellular growth of a virus be used to explore the behavior of mutant viruses that encode alternative designs? As a starting point, one can create alternative designs that reorder or rearrange the wildtype genes or regulatory elements. Such genomic changes can alter the timing and level of expression of different viral genes, and thereby impact growth because the production of viral progeny depends on the dynamic expression of viral genes. Preliminary models of such alternative genome designs can use the ''language'' of the wild-type virus. They retain the parameters that characterize wild-type molecular interactions, wild-type average rates of viral polymerase elongation, and wild-type composition of progeny viruses, but they apply them in a manner that reflects the reordering of wild-type components in the engineered genome. For example, the timing of expression for the genes of phage T7 during infection maps closely to their sequential order on the T7 genome [15, 16] . By relocating an essential early gene, encoding the T7 RNA polymerase to downstream positions, one delays initiation of transcription by the highly efficient T7 RNA polymerase and thereby attenuates phage growth [17] . Preliminary models for the growth of phage carrying the altered genomes, based on wild-type parameters, capture the overall observed trends in attenuation. Here we expand this approach to a mammalian virus of biomedical and agricultural relevance: vesicular stomatitis virus (VSV).