Zebrafish Hepatitis C Models

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.

Zebrafish as a model organism for HCV sub-replicon amplification.

Our Zebrafish Hepatitis C Models

Our zebrafish models partially mimic HCV activity in the human liver, with α-2-HS-glycoprotein, Hsp70, chemokine-1, leucine-rich repeats observed in HCV subreplicon-injected larvae Increases in genes such as G protein-coupled receptor 5 induced gene expression changes similar to those in human hepatocytes. In addition, our zebrafish Hepatitis C models can also be used to evaluate anti-HCV drugs or drug candidates. Overall, our zebrafish Hepatitis C models are novel and simple in vivo models for studying the pathology of HCV infection in the liver by the mechanism of HCV replication and can be used in drug evaluation studies to aid in the discovery of new anti-HCV drug.

Advantages

• Highly mimics HCV activity in human liver.
• Transparency of embryos allows use of sophisticated in vivo live imaging techniques.
• Accurate assessment of preventive and therapeutic strategies to combat HCV infection.
• Small size, high fecundity, and fast embryonic development make zebrafish suitable for modifier genetic screens.

References

1. Ding CB, et al. A zebrafish model for subgenomic hepatitis C virus replication. Int J Mol Med. 2015, 35(3):791-797.
2. Ding CB, et al. Zebrafish as a potential model organism for drug test against hepatitis C virus. PLoS One. 2011, 6(8):e22921.
3. Ploss A, et al. Towards a small animal model for hepatitis C. EMBO Rep. 2009, 10:1220–1227.
4. Lerat H, et al. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology. 2002, 122:352–365.
5. Dooley K, et al. Zebrafish: a model system for the study of human disease. Curr Opin Genet Dev. 2000, 10:252–256.

For research use only. Not intended for any clinical use.