Flaviviruses: Structure, Replication and Evolution (eBook)

Cover 1
Contents 6
Chapter 1. Taxonomy of the Virus Family Flaviviridae 16
I. Historical Perspective 16
II. Early Classification 18
III. Toward an Adequate Taxonomy 20
IV. Current Taxonomic Placement of Flaviviruses 22
References 32
Part 1: Structure and Replication 36
Chapter 2. Molecular Biology of Flaviviruses 38
I. Introduction 38
II. Viral Life Cycle 38
III. Flavivirus Particles 40
IV. Genome Structure 43
V. Virus Proteins 47
VI. RNA Replication 60
References 62
Chapter 3. Flavivirus Structure and Membrane Fusion 78
Preamble 78
I. Introduction 78
II. Assembly and Maturation 81
III. Structure of the E Protein 84
IV. Architecture of Recombinant Subviral Particles and Virions 87
V. Fusion Characteristics 89
VI. Low pH-Induced Structural Changes 90
VII. Interactions with Membranes 92
VIII. Function of the prM Protein 95
IX. Comparative Aspects of the Flavivirus Fusion Machinery 96
References 99
Addendum 106
References for Addendum 112
Chapter 4. Kunjin RNA Replication and Applications of Kunjin Replicons 114
I. Introduction 115
II. Foundations for Developing a Model of KUNV RNA Synthesis 116
III. Extending the Scope of Replication Analyses 118
IV. Ultrastructure of Induced Membranes, Their Association with the Replication Complex (RC), and Their Origins 122
V. Molecular Approaches to Study Formation and Operation of the RC 132
VI. Development of the Kunjin Replicon Expression System for Vaccines and Gene Therapy. 144
VII. Concluding Remarks 148
References 149
Chapter 5. Antigenic Structure of Flavivirus Proteins 156
I. Introduction 156
II. Classical Flavivirus Serology 157
III. B-Cell Epitopes 158
IV. T-Cell Epitopes 174
V. Conclusion 178
References 179
Chapter 6. 5'- and 3' -Noncoding Regions in Flavivirus RNA 192
I. Introduction 192
II. Conserved Linear Sequence Features of NCRs in Flavivirus RNA 196
III. Secondary Structure of NCRs. 218
IV. Mutational Changes in the 5' or 3' NCR and the 3' SL May Result in Attenuation of Virus Virulence 229
V. Hypothesis for Hydrogen Bonding between 5' and 3' NCRs 230
VI. Additional Secondary Structure Predictions in the 3' NCR 231
VII. Summary and Future Directions 234
References 238
Chapter 7. Manipulation of Cell Surface Macromolecules by Flaviviruses 244
I. Introduction 245
II. The Flavivirus Receptor Binding Protein 245
III. Cell Targets for Flaviviruses 247
IV. Cell Surface Macromolecules Involved in Flavivirus Attachment 257
V. Cell Surface Macromolecules Modulated by Flavivirus Infection 264
VI. Other Cell Surface Macromolecular Modifications Triggered by Flavivirus Infection 268
VII. Conclusions 270
References 270
Part 2: Flavivirus Evolution 290
Chapter 8. Origins, Evolution, and Vector/Host Coadaptations Within the Genus Flavivirus 292
I. Introduction 293
II. Phylogenetic Analysis of the Genus Flavivirus 296
III. Impact of Host/Virus Coadaptation on Flavivirus Evolution 300
IV. What Are the Origins of Flaviviruses? 319
V. Does Recombination Occur between Flaviviruses and, if so, What Is the Likely Impact? References 321
References 323
Chapter 9. Microevolution and Virulence of Dengue Viruses 330
I. Introduction 331
II. Genetic Variation within Dengue Serotypes 332
III. Phylogenetics of Dengue Viruses 333
IV. Viral Determinants of Disease 346
V. Viral Determinants of Transmission 349
VI. Viral Displacement and Epidemiology 350
References 351
Index 358
Color Plate Section 386