DNA microarray studies shed light on the transcription state of the cell but do not necessarily link specific gene products with the biological problem being addressed. Accordingly, it is important to test the roles of individual genes using other approaches. We will use in vitro assays of viral replication to study the roles of genes whose expression we have found to be altered in HCV infected liver. These are not straightforward experiments, since HCV is a difficult virus to study. HCV replicates only in humans and chimpanzees, and only poorly in isolated human peripheral blood cells, though these do act as an extrahepatic viral pool. Subgenomic RNA replicons can be transfected into certain cell lines and maintained, but to date only a few genotypes have been successfully translated into a replicon model (1b, 1a, and 2a). Recently, an elegant HCV model was described in Edmonton in which human hepatocytes are transplanted into SCID-beige mice. This model supports HCV infection and replication; however, since the bulk of HCV effects are due to the immune response generated by the virus, this model as it exists currently may not be ideal for studying how the virus leads to liver damage and evades antiviral immune responses in humans.