Modeling HCV disease in animals: Virology, immunology and pathogenesis of HCV and GBV-B infections
Hepatitis C virus (HCV) infection has become a global public health burden costing billions of dollars in health care annually. Even with rapidly advancing scientific technologies this disease still poses a significant threat due to a lack of vaccines and affordable treatment options. The immune correlates of protection and predisposing factors toward chronicity remain major obstacles to development of HCV vaccines and immunotherapeutics due, at least in part, to lack of a tangible infection animal model. This review discusses the currently available animal models for HCV disease with a primary focus on GB virus B (GBV-B) infection of New World primates that recapitulates the dual Hepacivirus phenotypes of acute viral clearance and chronic pathologic disease. HCV and GBV-B are also closely phylogenetically related and advances in characterization of the immune systems of New World primates have already led to the use of this model for drug testing and vaccine trials. Herein, we discuss the benefits and caveats of the GBV-B infection model and discuss potential avenues for future development of novel vaccines and immunotherapies. Hepatitis C virus (HCV) is a major chronic disease that has infected greater than 150 million people worldwide. Given the breadth and duration of infection HCV disease could result in an economic crisis reaching into the 100s of billions within the next decade. Although acute infection is usually asymptomatic with self-resolution, 55-85% of infected persons develop chronic disease that can lead to progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC; Hoofnagle, 2002) which is often fatal without treatment. There is also a strong association of HCV infection with extra-hepatic diseases such as cryoglobulinemia vasculitis (Luppi et al., 1998), diabetes (Mehta et al., 2000), thyroid disease (Pateron et al., 1992), lichen planus (Jubert et al., 1994), and neuropsychiatric conditions such as depression (Thomas, 2013). This is complicated by the fact that approximately only half of individuals are aware of their HCV status (Denniston et al., 2012), due, at least in part, to the rarity of symptoms in acute HCV infection. In 2007, mortality due to HCV infection surpassed that of HIV in the United States (Ly et al., 2012).
Manickam, C; Keith Reeves, R
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