Error-prone viruses such as hepatitis C virus, West Nile virus, and HIV are among the most successful pathogens on the planet and continue to challenge the development of therapies. Our laboratory studies how these errors are made, the effect of the errors on the viral population, how genetic recombination can re-assort mutations, and the effect of viral diversity on trafficking and pathogenesis in infected animals. We are interested in the contraction and expansion of the quasispecies, both within an infected animal and in transmission between infected animals. We are using hepatitis C virus, poliovirus, and yellow fever virus to study viral genome evolution, the acquisition of drug resistance mutations, genetic recombination, and the effect of viral diversity on pathogenesis. Our overall goal is to understand host and viral determinants of viral genome evolution, especially as they pertain to treatment failure.