Advances in Virus Research (eBook)

Front Cover 1
Advances in Virus Research 4
Copyright Page 5
Contents 6
Chapter 1: The Pathogenesis of Poliomyelitis: What We Don't Know 10
I. Introduction 12
II. Sequential Steps in the Spread of Infection 12
A. Questions unanswered: Cellular sites of replication 13
B. Questions unanswered: Neural invasion from the blood 15
III. Provocation Poliomyelitis 15
A. Questions unanswered: The mechanism of the provoking effect 16
B. Questions unanswered: Neural spread 19
IV. PVR, Tropism, and the Localization of Lesions 20
A. Questions unanswered: Receptor expression is necessary but not sufficient 20
B. Questions unanswered: Localization within the CNS 22
C. Questions unanswered: How poliovirus kills cells 24
V. Host Innate and Immune Response to Infection 24
A. Questions unanswered: The acquired immune response 25
VI. Immune Defenses and Viral Clearance: Mechanisms of Vaccine-Induced Protection 26
A. Primary infections 26
B. Secondary infection in immune hosts 27
C. Poliovirus serotypes 29
VII. Animal Models of Human Poliomyelitis 30
A. Questions unanswered: Determinants of primate susceptibility 31
B. Questions unanswered: The mechanism of rodent adaptation 32
C. Questions unanswered: PVR mice 34
D. Questions unanswered: The tropism enigma 35
VIII. Virulence of Polioviruses 35
A. Questions unanswered: Mechanisms of neurovirulence 41
B. Questions unanswered: Viremia and virulence 41
C. Questions unanswered: Epidemiological properties of polioviruses 42
IX. How Does Poliovirus Persist? 43
A. Questions unanswered: Overt persistence of poliovirus 44
B. The post-polio syndrome and covert persistence of poliovirus 44
X. Eradication 45
A. Questions unanswered: Why is it so difficult to complete the global eradication of wild polioviruses? 46
XI. Vaccine-Derived Polioviruses and the Eradication Endgame 47
A. Questions unanswered: What strategy should be followed if wild polioviruses are eradicated? 48
XII. Reprise 50
Acknowledgments 51
References 51
Chapter 2: Cutting the Gordian Knot-Development and Biological Relevance of Hepatitis C Virus Cell Culture Systems 60
I. Introduction 62
II. Genetic Heterogeneity of HCV-Genotypes, Subtypes, Isolates, and Quasispecies 63
III. The HCV Genome and Its Encoded Proteins 68
IV. Host Cell Factors Supporting the HCV Life Cycle 76
V. Consensus HCV cDNA Clones-Infectious in Transfected Chimpanzees 80
VI. The Replicon System-Autonomous HCV RNA Replication in Hepatoma Cell Lines 82
A. Identification of adaptive mutations led to more efficient replicon systems 83
B. The study of replicon systems led to identification of highly permissive Huh7 cell lines 87
VII. Pseudo-Particles Expressing the HCV Envelope Proteins (HCVpp)-A System for the Study of Viral Entry and Neutralization 88
VIII. The JFH1 Isolate-Generation of Cell Culture Derived HCV (HCVcc) in Full Viral Life Cycle Cell Culture Systems 91
A. The original and adapted JFH1 cell culture system 91
B. The J6/JFH1 cell culture system 96
C. Analysis of HCV buoyant density suggests a role of lipoproteins for the viral life cycle 98
D. Possible causes of special growth characteristics of JFH1 and J6/JFH1 100
E. Applicability of JFH1 and J6/JFH1 cell culture systems 101
IX. Perspectives for Further Development of HCV Cell Culture Systems 104
A. Adaptation of cell culture systems to yield higher viral titers 104
B. Cell culture systems for other HCV genotypes 104
C. Expansion of cell culture systems to different host cells 109
X. Conclusion-Implications of Novel Cell Culture Systems 112
Acknowledgments 113
References 113
Chapter 3: Poxvirus Host Range Genes 144
I. Introduction 145
II. Orthopoxvirus Host Range Genes 146
A. SPI-1 149
B. K1L 152
C. C7L 154
D. CHOhr 155
E. p28/N1R 156
F. B5R (ps/hr) 157
G. E3L 158
H. K3L 161
III. Myxoma Virus Host Range Genes 162
A. M-T2 163
B. M-T4 164
C. M-T5 164
D. M11L 166
E. M13L 167
F. M063 168
IV. Molluscum Contagiosum: An Extreme Example of Host Range Restriction 169
V. Conclusions 169
Acknowledgments 171
References 172
Chapter 4: Receptor Interactions, Tropism, and Mechanisms Involved in Morbillivirus-Induced Immunomodulation 182
I. Introduction 183
A. General aspects of MV- and morbillivirus-induced immunosuppression 185
B. Relationships between tropism of the virus, spread of infection, and immunosuppression 186
II. Leukopenia Associated with Morbillivirus Infections 190
III. Mechanisms and Consequences of T Cell Silencing in Morbillivirus Infections 192
IV. Receptors and Signaling Involved in Suppression of Cell Functions 195
V. Virus Interactions with DCs 199
A. Virus interference with DC functions in animal models 199
B. Experimental models and consequences of DC surface interactions with viral proteins 200
C. Consequences of infection on DC viability and function 201
VI. Conclusions and Perspectives 204
References 205
Chapter 5: Lyssaviruses-Current Trends 216
I. Introduction 217
II. Developments in Diagnostic and Surveillance Tools 218
A. Diagnosis 218
B. Viral typing 219
C. Evolutionary time frames 220
D. Modeling applications 221
III. Fundamental Aspects of Virus-Host Interactions 222
A. What is the basis for RABV pathogenicity? 223
B. Role of viral proteins 223
C. Role of host cell pathways 227
D. Considerations for future studies on rabies pathogenesis 231
IV. Reverse Genetics-Methodology and Applications 231
A. RABV vaccines 233
B. Vaccines for other diseases 234
V. Other Strategies for Rabies Vaccine Development 236
A. Adenovirus recombinants 236
B. DNA vaccines 237
VI. The Challenge of Rabies Biologics for Passive Immunity 239
VII. Novel Applications of RABV 240
A. Use as a neuronal tracer 240
B. Use of RABV proteins for molecular targeting 244
VIII. Concluding Remarks 245
References 246
Index 260
Color plate section 266