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About the Authors:
Abeba Tesfaye
* E-mail: [email protected]
Affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, United States of America
Judith Stift
Affiliation: Institute of Pathology, Medical University of Vienna, Wien, Austria
Dragan Maric
Affiliation: Division of Intramural Research, Flow Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
Qingwen Cui
Affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, United States of America
Hans-Peter Dienes
Affiliation: Institute of Pathology, Medical University of Vienna, Wien, Austria
Stephen M. Feinstone
Affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, United States of America
Introduction
Hepatitis C is a major public health problem that affects an estimated 180 million people worldwide. In the US alone, there are nearly 3 million HCV infected patients [1]. Chronic HCV infected patients are at risk of developing chronic liver disease, cirrhosis and eventually liver cancer [2-4]. The virus has a single strand, plus sense RNA genome with an envelope derived from host cellular membranes. There are six major genotypes of the hepatitis C virus with additional subtypes [5] but it is not known if these genotypes also relate to serotype diversity. The virus has a limited host range of humans and chimpanzees and the chimpanzee remains the only complete animal model for HCV infection and disease that can be used in studies of pathogenesis of hepatitis C virus and immune response to infection or for preclinical evaluation of developmental vaccines [6,7]. While there is no vaccine to prevent hepatitis C virus infections [8], antiviral treatment with alpha interferon and ribavirin is effective in actually curing the infection in up to fifty percent of patients with chronic HCV. The addition of newer, direct acting antiviral agents can improve the outcome of treatment to over eighty percent [9-11].
Over the past few years, several transgenic mouse models have been developed that support the replication of HBV and HCV. The successful infection of chimeric mice in which the diseased mouse livers were repopulated by human hepatocytes was reported beginning in 2001 [12-14]. These immunodeficient mice (SCID/Bg) carry an array of tandem copies of the transgene...