HCV Infection/Transfection Of Tree Shrews In Vivo

Hepatitis C virus (HCV) is a human hepatotropic virus that causes acute and chronic hepatitis and hepatocellular carcinoma. Our understanding of the immune response to HCV is incomplete, largely due to the narrow host restriction of this pathogen and the limitations of existing experimental models. Much of our current understanding of the HCV life cycle is derived from studies of HCV-infected chimpanzees, and HCV transgenic mice. However, chimpanzee experiments are limited by cost, availability, and ethical considerations, whereas transgenic mice are immunologically tolerant to the virus, thereby compromising the greatest potential strength of an animal model of HCV infection. Tree shrew is a primate-related animal which can be infected by some human relative viruses. Recently, studies demonstrated that tree shrew hepatic cells could support the replication of HBV and HCV. Thus the tree shrew may be a potential alternative for HCV in vivo studies.Objective:In order to explore the possibility that tree shrew can be infected by HCV, we use the full-length infectious HCV RNA synthesized in vitro and HCV from human serum to transfect and infect tree shrews in vivo. Then we dynamically observe the transform of tree shrews postinoculation. Methods:21 adult wild tree shrews from Yunnan province were artificially breeded and inoculated the infectious HCV RNA or the human HCV RNA serum positive through femoral vein respectively. Serum HCV loads, and anti-HCV, as well as ALT level were dynamically after inoculation. Liver pathology was evaluated.Results:1. HCV RNA was detected intermittently in the serum of all infected or transfected animals.2. The serum ALT levels of all experimental groups in different time point emerged fluctuation and significantly higher than the average before inoculation. Moreover, the titer of HCV in serum obviously correlates with the abnormall rate of ALT.3. Histological examination of liver biopsies revealed slight inflammatory changes in some of infected animals.4. The infection effect of full-length HCV RNA was similar as compaired to human serum derived HCV.5. Part of the tree shrews emerge temporal anorexia and loose stool, but they show no significant changes of body weight after inoculation.Conclusion:Tree shrews could be infected with HCV. The infection effect of full-length HCV RNA was similar with that of human serum derived HCV. Tree shrews may be a potential susceptible animal to HCV, allowing foundmental and clinical studies related to HCV infection.