1 Comparative and Historical Aspects of the Togaviridae and Flaviviridae.- I. Introduction.- II. Yellow Fever.- A. Early History.- B. Carlos J. Finlay and the Walter Reed Commission.- C. Yellow Fever Commissions of the Rockefeller Foundation.- D. Asibi Virus and the 17D Yellow Fever Vaccine.- III. Early Studies on Viral Encephalitides.- IV. Arthropod-Borne Viruses.- A. Antigenic Relationships among Arboviruses.- B. Serological Groups A and B.- V. Viral Classification and Nomenclature.- VI. Arbovirus Study Group: Togaviruses and Togaviridae.- VII. Non-Arthropod-Borne Togaviruses.- VIII. Contribution of the World Health Organization.- IX. Contribution of the American Committee on Arthropod-Borne Viruses.- X. Impact of Molecular Biology on Viral Classification.- XI. Flaviviridae as a Separate Family.- References.- 2 Alphavirus Structure.- I. Introduction.- II. General Properties.- A. Radial Organization.- B. Glycoprotein Shell.- C. Lipid Bilayer.- D. Core (Nucleocapsid).- E. Hexagonal Glycoprotein Arrays.- III. Virion Assembly.- References.- 3 Structure and Replication of the Alphavirus Genome.- I. Introduction.- II. Structure of the Alphavirus Genome.- A. Physical Structure.- B. Genome Organization.- III. Nonstructural Proteins.- A. Translation and Processing.- B. Opal Codon.- C. Functions of Nonstructural Proteins.- IV. Structural Proteins.- A. Translation and Processing.- B. Functions of Structural Proteins.- C. Mapping of Temperature-Sensitive Mutants.- V. Replication and Transcription of Viral RNA.- A. In Vivo Studies of RNA Replication.- B. In Vitro Studies of RNA Replication.- C. Genetic Studies of Replicase Functions.- D. Host-Cell Proteins as Components of the Viral Replicase.- E. Conserved Sequences in Alphavirus RNAs.- F. Cyclization of Alphavirus RNAs.- G. Alphavirus Defective Interfering RNAs.- VI. Evolution of the Alphavirus Genome.- A. Evolution within the Genus Alphavirus.- B. Codon Usage in Alphaviruses.- C. Evolution within the Family Togaviridae.- D. Relationship of Alphaviruses to Other RNA Viruses.- VII. Concluding Remarks.- References.- 4 Entry of Alphaviruses.- I. Introduction.- II. Attachment.- III. Endocytotic Uptake and Penetration.- A. Cell Biology of Endocytosis.- B. Endocytosis of Viruses.- C. Role of Endosomes in Virus Penetration.- IV. Inhibition of Entry.- A. Lysosomotropic Weak Bases.- B. Carboxylic Ionophores.- C. Monovalent Cations.- D. Temperature Effects.- V. Acid-Dependent Membrane Fusion.- A. Properties of Fusion.- B. Acid-Induced Conformational Change in the Viral Spike Glycoproteins.- C. Mechanism of Fusion.- VI. Conclusion.- References.- 5 Formation and Assembly of Alphavirus Glycoproteins.- I. Glycoprotein Structures and Domains.- II. Biosynthesis of Polypeptides.- III. Glycosylation.- A. Synthesis and Structure of the Oligosaccharide Chains.- B. Role of Glycosylation in Virion Formation.- IV. Fatty Acid Acylation.- V. Proteolytic Formation of E2.- VI. Localization of Glycoproteins to Intracellular Organelles.- VII. Expression of Virus Glycoproteins from Complementary DNAs.- VIII. Assembly and Budding of Virus.- A. Nucleocapsid Formation.- B. Interactions at the Plasma Membrane.- IX. Conclusions and Perspectives.- References.- 6 Defective RNAs of Alphaviruses.- I. Introduction.- II. Identification of Sequences Retained in the Defective Interfering Genomes of Sindbis and Semliki Forest Viruses.- A. Characterization of the Defective Interfering RNAs.- B. Sequence Organization of Defective Interfering RNAs of Sindbis and Semliki Forest Viruses.- C. Expression of Cloned Defective Interfering Genomes.- III. Defective Interfering Particles of Alphaviruses and Persistent Infections.- A. Characteristics of Persistent Infections in Mammalian Systems.- B. Evolution of Sindbis Virus and Its Defective Interfering RNAs during Persistent Infection of Baby Hamster Kidney Cells.- IV. Defective Interfering Particles as a Probe for Analysis of Viral Replication and Identification of Host Factors.- A. Generation and Accumulation of Defective Interfering Particles in Different Host Cells.- B. Biological Heterogeneity among Alphavirus Defective Interfering Particles.- V. Conclusion.- References.- 7 Replication of Alphaviruses in Mosquito Cells.- I. Introduction.- II. Growth of Alphaviruses in Whole Insects and Insect Larvae.- III. Development of Cell Cultures for Use in Studies of Alphavirus-Insect Cell Interactions.- IV. Early Events in the Infection of Cultured Insect Cells with Alphaviruses.- V. Development of Alphaviruses during Acute Infection of Insect Cells.- A. Kinetics of Virus Production.- B. Synthesis of Viral RNA and Protein.- C. Assembly and Maturation of Alphavirus.- D. Cell Response to Alphavirus Infection.- VI. Role of Insect Host-Cell Functions in the Reproduction of Alphaviruses.- VII. Establishment and Maintenance of Persistent Alphavirus Infections of Insect Cells.- A. Transition from Acute to Persistent Infection.- B. Role of Temperature-Sensitive Mutants and Defective Interfering Particles in the Establishment of Persistent Infection.- C. Appearance and Function of Antiviral Compounds.- VIII. Conclusions and Perspectives.- References.- 8 Alphavirus Pathogenesis and Immunity.- I. Introduction.- II. Disease Pathogenesis.- A. Eastern Equine Encephalitis.- B. Western Equine Encephalitis.- C. Sindbis Virus.- D. Venezuelan Equine Encephalitis.- E. Semliki Forest Virus.- F. Chikungunya and O'nyong-nyong Viruses.- G. Ross River Virus.- III. Development of the Immune Response.- A. Natural Immunity.- B. Virus-Specific Immunity.- IV. Summary.- References.- 9 The Use of Monoclonal Antibodies in Studies of the Structural Proteins of Togaviruses and Flaviviruses.- I. Introduction.- II. Alphaviruses.- A. Serology and Classification of Alphaviruses.- B. Antigenic Mapping of Alphavirus Structural Proteins Using Monoclonal Antibodies.- C. Alphavirus Immunity.- D. Monoclonal Antibodies in Alphavirus Serology and Epidemiology.- E. Vaccine Strategy.- III. Flaviviruses.- A. Serology and Classification of Flaviviruses.- B. Antigenic Mapping of Flavivirus Structural Proteins Using Monoclonal Antibodies.- C. Flavivirus Immunity.- D. Monoclonal Antibodies in Flavivirus Serology and Epidemiology.- E. Vaccine Strategy.- IV. Other Viruses.- V. Assessment of Future Research Goals.- References.- 10 Structure of the Flavivirus Genome.- I. Introduction.- II. Physical Structure of the Genome.- III. Genome Organization.- A. Gene Order.- B. Translation Strategy.- C. Proteolytic Cleavages in Processing of Flavivirus Proteins.- IV. Characteristics of Flavivirus Proteins from Sequence Data.- V. Structures in the Flavivirus Genome.- VI. Evolution of Flaviviruses.- VII. Concluding Remarks.- References.- 11 Replication of Flaviviruses.- I. Introduction.- II. Virion Morphology and Composition.- A. Morphology.- B. Physicochemical Properties and Chemical Composition.- C. Structural Proteins.- D. Genome RNA.- III. Infection of Cultured Cells.- A. Effect on Host-Cell Macromolecular Synthesis.- B Immune Enhancement.- IV. Viral Morphogenesis.- A. Intracellular Sites of Viral Macromolecular Synthesis.- V. Viral RNA Synthesis.- VI. Viral Protein Synthesis.- VII. Genetically Controlled Resistance to Flaviviruses.- VIII. Defective Interfering Particles.- IX. Persistent Infections.- X. Flavivirus Mutants.- XI. Summary.- References.- 12 Pathology of the Flaviviruses.- I. Introduction.- II. Medical Importance of the Flaviviruses.- III. Pathobiological Significance of Natural Virus Variation and Heterogeneity.- IV. Pathogenesis of Flaviviral Encephalitis.- A. Host Factors That Influence Pathogenesis.- B. Major Aspects of Pathogenesis.- C. Immune Responses.- V. Pathogenesis of Flaviviral Hemorrhagic Fevers.- A. Comparative Pathology.- B. Sites of Viral Replication.- C. Pathogenesis of Dengue Hemorrhagic Fever/Dengue Shock Syndrome.- D. Yellow Fever: Pathophysiological Correlations.- E Immune Modulation, Suppression, and Lymphocytolysis.- F.
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Persistent and Congenital Infections.- G. Genetic Host Resistance.- References.