Models of Viral Hepatitis (Monographs in Virology, Vol. 25)

Viral hepatitis B or C is the most common cause of chronic liver disease worldwide and accounts for about 80% of all hepatocellular carcinoma cases. Thus, combating viral hepatitis remains one of the most pressing public health issues today. Animal models and cell-based systems are essential tools for addressing the many still unresolved basic and clinical problems. Experimental models are needed to better understand the viral life cycles, pathogenetic aspects and natural defense mechanisms, while preclinical models are required for evaluating novel preemptive and therapeutic strategies. This monograph provides a unique synopsis of currently available models of viral hepatitis, highlighting their particular use for basic and translational science. Leading experts discuss new scientific results and evolving methods in various animal and in vitro models, including the woodchuck, duck, mouse, chimpanzee and tupaia, as well as primary hepatocytes and subgenomic HCV replicons. A valuable single source of information, this book will be of interest to all investigators and clinicians working in the fields of viral hepatitis and/or hepatology. Contents......Page 6 Foreword......Page 8 The Woodchuck: A Model for Immunopathogenesis and Therapy of Hepadnaviral Infection......Page 10 The Immune System of the Woodchuck......Page 11 Cytokines......Page 12 Cell Surface Markers......Page 14 MHC Class II......Page 16 Characterization of Specific T-Cell Immune Response to WHV in the Woodchuck......Page 17 Kinetics of T-Cell Response during Incubation Period and Acute Phase of WHV Infection......Page 18 Mapping of T-Helper Epitopes......Page 19 Failure of Appropriate Immune Response in the Incubation Period and Early Acute Infection Results in Chronic Carrier Status......Page 21 Treatment of Chronic WHV Infection......Page 23 Adenoviral Vector-Mediated Cytokine Expression in Liver......Page 24 Adoptive Immunotransfer by Liver Transplantation in the Woodchuck Model......Page 25 Conclusions......Page 27 References......Page 28 Pathogenesis of Hepatitis B Virus in Transgenic Mice......Page 34 Antiviral Mechanisms......Page 35 Immunopathological Mechanisms......Page 37 References......Page 39 Transfer of HBV Genomes into Mice......Page 42 HBV Genome Transfer using Adenoviral Vectors......Page 44 Alternative Models of HBV Infection......Page 46 References......Page 48 The Avian Hepadnaviruses......Page 51 Species Specificity of Hepadnavirus Infection......Page 52 Features of DHBV Particles and Viral Replication......Page 53 DHBV-Infected Ducks as a Model for Human HBV Infection......Page 54 Studies of a DHBV X Protein Knockout Strain......Page 55 Studies of a Cytopathic Mutant of DHBV......Page 56 Liver Damage and Persistent DHBV Infection......Page 57 The Role of the Immune Response in the Resolution of Transient DHBV Infection......Page 58 Virus Infection Persists after the Apparent Resolution of Transient DHBV Infection......Page 60 Combining Antiviral and Novel DNA Vaccines for Treatment of Persistent HBV Infections......Page 61 References......Page 62 Determinants of Hepadnaviral Species and Liver Cell Tropism......Page 65 Host Tropism and Species Specificity......Page 66 Infectious Entry......Page 68 Intracellular Trafficking......Page 72 References......Page 73 T-Cell Response to Hepatitis B and C Virus: Lessons from the Chimpanzee Model......Page 75 T-Cell Response to HBV in Humans......Page 76 Analysis of a Successful Immune Response against HBV......Page 77 CD8+ T Cells but not CD4+ T Cells Mediate Viral Clearance and Disease Pathogenesis during Acute HBV Infection......Page 78 Courses of Acute HCV Infection in Chimpanzees......Page 81 Analysis of Successful Immune Responses against HCV......Page 82 Mechanisms of Viral Persistence during Acute HCV Infection in Chimpanzees......Page 84 Protective Immunity......Page 86 Acknowledgments......Page 87 References......Page 88 The Replicon System as an Efficient Tool to Study HCV RNA Replication......Page 90 Principles of the Replicon System and Properties of Selected Cell Clones......Page 91 Determinants of Replication Efficiency of the Con1 Isolate......Page 92 HCV Isolates Successfully Used in the Replicon System......Page 94 Cell Lines Permissive for HCV Replicons......Page 96 Applications of Replicon Cell Clones and Transient Replication Assays......Page 97 Perspectives and Limitations......Page 99 Acknowledgement......Page 100 References......Page 101 Hepatitis B Virus Infection of Primary Tupaia Hepatocytes......Page 105 References......Page 113 Tupaia belangeri as a Model for Hepatitis C Virus Infection......Page 115 In vitro Model Systems......Page 117 HCV Infection of T. belangeri in vivo......Page 118 In vitro HCV Infection of Primary Tupaia Hepatocytes......Page 119 References......Page 123 Primary Human Hepatocytes as an in vitro Model for Hepatitis B Virus Infection......Page 128 Hepatocyte Donors and Cell Isolation Procedure......Page 129 Culture Conditions for Primary Hepatocytes......Page 130 Conditions for in vitro HBV Infection......Page 131 Detection of in vitro HBV Infection......Page 132 Quantification of Viral Antigen and DNA Production......Page 133 Standardization of in vitro HBV Infection......Page 134 Viral Attachment and Cellular Receptor Studies......Page 136 Analysis of Antiviral Effects of Cytokines......Page 137 Interaction of Infected Hepatocytes and Immune Effector Cells......Page 138 Conclusions and Future Aspects......Page 139 References......Page 141 Hepatocyte Transplantation......Page 144 Transplantation of Adult Human Primary Hepatocytes......Page 145 HBV Infection of Transplanted Hepatocytes in Mice......Page 147 Hepadnaviral Infection of Mice Repopulated with Tupaia Hepatocytes......Page 148 Cryopreservation and Transplantation of Frozen Primary Hepatocytes......Page 150 Further Applications......Page 151 References......Page 152 The Trimera Mouse Model of HBV and HCV Infection......Page 155 The Humanized Trimera Mouse Model......Page 157 HBV/HCV Replication in the Trimera......Page 159 Induction and Characterization of Human Immune Responses in the Trimera......Page 161 The Trimera Compared to Different HBV and HCV Animal Models......Page 165 References......Page 166 H......Page 170 T......Page 172 W......Page 173 Annotation "This monograph provides a unique synopsis of currently available models of viral hepatitis, highlighting their particular use for basic and translational science. Leading experts discuss new scientific results and evolving methods in various animal and in vitro models, including the woodchuck, duck, mouse, chimpanzee and tupaia, as well as primary hepatocytes and subgenomic HCV replicons."--BOOK JACKET. Title Summary field provided by Blackwell North America, Inc. All Rights Reserved