Main description:

2. Virological Findings. 90 3. Immunity. . . . . 90 C. Secondary Dengue: Dengue Hemorrhagic Fever and the Shock Syndrome 92 1. General Remarks. . . . . . . . . . . . . . 92 2. Clinical Course and Clinical Laboratory Findings 93 3. Virological and Serological Findings. . . 95 4. Immunopathology of Secondary Dengue. 98 XI. Immunization. . . . . . . . . . . . . . . 104 A. Anamnestic Immune Responses in Sequential Infections With Dengue and Other Group B Togaviruses . . . . . . . . 104 1. Results With Members of the Dengue Subgroup 104 2. Results With Dengue and Other Flaviviruses. 107 B. Dengue Vaccines for Use in Man 108 XII. Opportunities for the Future 113 Acknowledgments. 114 References. . . . . . . . . . . 114 I. Introduction Dengue fever is a mosquito-transmitted disease of man which has afflicted untold millions of people over the past two centuries. It is caused by viruses classified as a subgroup of the group B togaviruses. Along with other members of that group as well as group A, the dengue viruses have been investigated intensively during recent years. Certain unique aspects of their structure, composition, antigenicity, replication, and antigenic relationships have established the togavirus family as quite distinct from other families of enveloped RNA viruses (see recent review of PFEFFERKORN and SHAPIRO, 1974). The basic studies leading to this conclusion have coincided with epidemiological field investigations which have resulted in a continuing increase in the number of viruses now designated as group A or B togaviruses. This, in turn, has led to a growing appreciation of their immense importance as actual or potential pathogens of man and beast.

Contents:

I. Introduction.- II. Definitions and Nomenclature.- III. History.- IV. Classification.- V. Biological Systems Used to Study Basic Viral Properties.- A. Host Systems Serving as Sources of Virus.- 1. Man.- 2. Mouse.- 3. Mosquitoes.- 4. In vitro Cell Cultures.- B. Assay Procedures.- 1. Infectivity Assays.- a) Mice.- b) In vitro Cell Cultures.- c) Mosquitoes.- 2. Hemagglutination.- C. Serological Procedures.- 1. Neutralization.- a) In Mice.- b) Plaque Reduction.- 2. Hemagglutination Inhibition (HI).- 3. Complement Fixation (CF).- 4. Immunodiffusion.- VI. Properties of the Dengue Virion.- A. Size and Morphology.- 1. Filtration.- 2. Electron Microscopy.- B. Purification.- 1. Preliminary Extraction and Precipitation of Virus-Containing Materials.- 2. Preparative Centrifugation.- 3. Gradient Centrifugation.- C. Chemical Composition.- 1. Lipids.- 2. Viral RNA.- 3. Viral Structural Proteins.- 4. Carbohydrates.- D. Biological Activities of Viral Components.- 1. Infectious Viral RNA.- 2. Hemagglutinating "Subunits".- E. Antigenic Structure.- 1. Group-Specific Antigens.- 2. Subgroup (Dengue)-Specific Antigens.- 3. Type- and Strain-Specific Antigens.- 4. Non-Structural Dengue Antigens.- F. Reactions to Physical and Chemical Agents.- VII. Viral Replication in Cell Cultures.- A. Vertebrate Cells.- 1. The Viral Growth Cycle.- 2. Effects on Cells.- a) Morphological Changes Associated With Virus Replication.- b) Effects on Cellular Metabolism.- 3. Effects of Metabolic Inhibitors.- a) Inhibitors of RNA Synthesis.- b) Inhibitors of Protein Synthesis.- 4. Viral RNA Replication.- a) Rate.- b) Mechanism of RNA Replication.- 5. Synthesis of Virus-Specific Proteins.- 6. Viral Morphogenesis.- a) Current Ideas and Possible Alternatives.- b) Different Forms of Virus-Specific Particles.- B. Mosquito Cells.- C. Critical Summary Regarding Morphogenesis, Maturation and Release of Dengue Virions.- D. Persistently Infected Cell Cultures.- E. Interference and Interferon Production.- VIII. Pathogenesis (Experimental Hosts).- A. Monkey.- B. Mouse.- C. Other Mammals.- D. Chick Embryos.- E. Mosquitoes.- IX. Viral Variation, Genetics.- A. The Evolution of Neurovirulence.- B. Attenuation of Human Pathogenicity.- X. Essential Clinical Features.- A. General Considerations.- B. Primary "Classical Dengue Fever".- 1. Clinical Course and Clinical Laboratory Findings.- 2. Virological Findings.- 3. Immunity.- C. Secondary Dengue: Dengue Hemorrhagic Fever and the Shock Syndrome.- 1. General Remarks.- 2. Clinical Course and Clinical Laboratory Findings.- 3. Virological and Serological Findings.- 4. Immunopathology of Secondary Dengue.- XI. Immunization.- A. Anamnestic Immune Responses in Sequential Infections With Dengue and Other Group B Togaviruses.- 1. Results With Members of the Dengue Subgroup.- 2. Results With Dengue and Other Flaviviruses.- B. Dengue Vaccines for Use in Man.- XII. Opportunities for the Future.- Acknowledgments.- References.