HCV variants are described. The variants include polynucleotides comprisingnon-naturally occurring HCV sequences and HCV variants that have atransfection efficiency and ability to survive subpassage greater than HCVthat have wild-type polyprotein coding regions. Expression vectors comprisingthe above polynucleotides and HCV variants are also described, as are theprovision of cells and host cells comprising the expression vectors. Methodsfor identifying a cell line that is permissive for infection with HCV are alsoprovided, as are vaccines comprising the above polynucleotides in apharmaceutically acceptable carrier. Additionally, methods for inducingimmunoprotection to HCV in a primate are described, as are methods for testinga compound for inhibiting HCV replication.