Animal models for the study of hepatitis C virus infection and replication
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.World Journal of Gastroenterology (Impact Factor: 2.37). 06/2012; 18(23):2909-13. DOI: 10.3748/wjg.v18.i23.2909
Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.
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- "(2) Some of the clinically most relevant viruses infect the liver in a species-specific way, impeding the use of animal models. For example, infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) remain a global burden (Guha et al., 2004; MacArthur et al., 2012). Adenovirus is another pathogen which may infect the liver and cause severe medical problems, particular in immunocompromised individuals (Hough et al., 2005). "
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- "Although we have recently begun adding other human and hepatocyte-derived cell culture systems to the predominant Huh7-derived cell lines, non-human – particularly murine – cell lines remain a critical stepping-stone to animal model development. A series of efforts using knockout mouse cells, selectable virus replicons, and human factor transduction has recently culminated in multiple research groups achieving the complete virus life cycle in mouse cells expressing the required entry and liver factors , , , but animal models of HCV infection are still limited . HCV mouse models relying on SCID-uPA mice supporting xenografted human liver tissue can be infected, and virus-induced pathogenesis or drug response studied, but the mice have limited life spans, lack immune systems, and are expensive to produce . "
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- "Progress in mouse genetic manipulation and the valuable information gathered from studies performed in vitro and in the clinic have facilitated the development of chimeric models where immune-deficient mice are grafted with human hepatocytes (reviewed in Chayama et al., 2011; MacArthur et al., 2012). A more recent highlight, stemming from the progress in gene manipulation, is the generation of a humanized mouse model that can be infected by HCV (Dorner et al., 2011). "
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