facilitators
Hepatitis C virus (HCV) can cause hepatocellular carcinoma by directly integrating and destroying cancer-related genes such as TERT. Chronic HCV infection also causes inflammation and oxidative stress, which can lead to fibrosis and cirrhosis. However, the elucidation of the pathogenesis of HCV-related liver disease has been hindered by the lack of suitable small animal models. Although progress is currently being made in mouse models of HCV, the results are far from satisfactory. Establishing a mouse model of HCV infection requires surgical inoculation of human hepatocytes into recipient organs. Difficulties in using these models include complex surgical procedures, genetic variation in clinical HCV isolates, low and/or unstable HCV infection rates, and low HCV viremia.
The zebrafish has attracted attention as a vertebrate in the selection of host receptors for the HCV subreplicon. Zebrafish share good genetic homology with humans, particularly in the liver, and zebrafish hepatocytes may contain a biological environment compatible with human HCV replication that typically occurs in human hepatocytes. Furthermore, the HCV subreplicon replicates actively and stably in zebrafish tissue, and the procedure for generating subreplicon-positive larvae is straightforward. Because zebrafish are small and easy to manipulate in the laboratory, this small biological model is also suitable for drug screening against HCV.