Animal models for the study of HCV

Abstract

The development and evaluation of effective therapies and vaccines for the hepatitis C virus (HCV) and the study of its interactions with the mammalian host have been hindered for a long time by the absence of suitable small animal models. Immune compromised mouse models that recapitulate the complete HCV life cycle have been useful to investigate many aspects of the HCV life cycle including antiviral interventions. However, HCV has a high propensity to establish persistence and associated histopathological manifestations such as steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Better understanding of these processes requires the development of a permissive and fully immunocompetent small animal model. In this review we summarize the in vivo models that are available for the study of HCV.

Figure 1. Different approaches to study HCV in animal models

First panel: HCV-related viruses that infect animal species such as wild mice, rats, tamarins, bats and horses. These infections can be studied in their natural host, or eventually immune competent laboratory inbred mouse strains. Second panel: in vitro adaptation of HCV to mouse hepatoma cells may allow the isolation of viral variants that can establish an infection in wild type mice. Third panel: transient or stable expression of human factors that are essential to support infection of wild type HCV. Fourth panel: in xenotransplantation models, the genetic background of the host permits repopulation of the liver upon transplantation of human hepatocytes. Additional transplantation of HLA-compatible hematopoietic stem cells results in dually reconstituted mice.