Models of viral hepatitis

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