HEPATITIS-C VIRUS VIREMIA IN SCID-]BNX MOUSE CHIMERA

Chimpanzees are currently the only nonhuman animal model for reproduci ble propagation of hepatitis C virus (HCV). A chimeric mouse model was used for the induction of hepatitis C viremia, using BNX (beige/nude/ X-linked immunodeficient) mice preconditioned by total body irradiatio n and reconstituted with SCID mouse bone marrow cells. HCV-infected li ver fragments from patients with HCV RNA-positive sera were transplant ed under the kidney capsule of the chimeric mice, HCV-specific RNA seq uences were detected by reverse transcriptase nested polymerase chain reaction (RT-PCR) in serum of similar to 50% of grafted animals. In ad dition, normal liver specimens were incubated with HCV serum and trans planted into chimeric mice, leading to viremia in similar to 25% of an imals. Sequential histologic evaluation of the liver implants, from da y 2 to week 14 after transplantation, revealed loss of lobular archite cture within the implants. However, viremia persisted for 10-50 days a fter transplantation. These results offer a new HCV model.