Although human CD81 has been shown to be essential for hepatitis C Virus (HCV) infection, non-hepatic cells or transgenic animals expressing human CD81 alone did not support HCV replication. Co-expression of other cofactors was thus necessary for HCV replication. Previously, a hepatic factor named Sip-L was found to support HCV replication in an otherwise non-permissive cell line. To understand the species specificity of hepatic factors required for HCV replication, mouse hepatoma cells co-expressing human CD81 and Sip-L (Hepa1-6-CD81-Sip-L cells) were subjected for HCV infection assay. It was discovered that Hepa1-6-CD81-Sip-L cells were permissive for HCV infection and replication. An animal model was thus established by subcutaneous injection of the permissive cells into nude mice to generate tumors. Viral passages could be achieved in these animals. The antiviral effects of interferon and sodium stibogluconate administrated as a single agent or in combination were demonstrated in this animal model. (C) 2008 Elsevier Inc. All rights reserved.