Excerpt

Fifteen years ago, the drive to study retroviruses was rooted principally in the traditional goal of using animal models to understand human cancer. The historical importance of retroviruses in the discovery of cancer genes is now widely appreciated, but many of the recent spectacular revelations about the molecular basis of cancer have occurred in other venues—such as human genetics, cell signaling, and developmental biology—rather than virology. Instead, the central goals of retrovirology today are the treatment and the prevention of AIDS and the use of retroviruses as gene delivery devices. These goals have only intensified the need to further dissect viral particles and genomes, understand their modes of replication, and describe host responses to infection. Such efforts have focused on structural properties of viral proteins and their assembly; host receptors for retroviruses and their interactions with envelope proteins; the mechanism of proviral integration; the regulation of viral gene expression; and various aspects of pathogenesis and the immune response to retroviral infection.

Not surprisingly, recent efforts to examine these issues have focused largely on the HIVs and the retroviruses most commonly used to create vectors, the murine leukemia viruses (MLVs). It is our contention, and an assumption on which this book is built, that a full understanding of any single retrovirus depends on an appreciation of the common properties of retroviruses as a class, as well as the unique features of each type.

Contents

• Homage to Howard Temin
• Preface
• Acknowledgments
• Contributors
• Historical Introduction to the General Properties of Retroviruses
  PK Vogt.
  • The Place of Retroviruses in Biology
  • A Brief Chronicle of Retrovirology
  • The Development of Retrovirology as Intellectual History
  • Coda
  • References
• Retroviral Virions and Genomes
  VM Vogt.
  • Purification, Composition, and Morphology of Virions
  • Genetic Organization
  • Virion RNA
  • Organization of Genes in Prototypic Retroviruses
  • Taxonomy and Sequence Relatedness of Retroviruses
  • Virion Proteins
  • Models for Virion Structure
  • Frontiers
  • References
• Viral Entry and Receptors
  E Hunter.
  • Receptors
  • Retroviral Env Gene Products: Receptor Binding and Host-Range Determinants
  • Membrane Fusion and Viral Entry
  • Receptor-Mediated Barriers to Retroviral Infection
  • Conclusions
  • References
• Reverse Transcriptase and the Generation of Retroviral DNA
  A Telesnitsky and SP Goff.
  • Overview of Reverse Transcription
  • Reverse Transcription of the Viral Genome in vivo
  • Biochemistry of Reverse Transcription
  • Special Biological Features of Reverse Transcription
  • Conclusions
  • References
• Integration
  PO Brown.
  • Outline of the Integration Process
  • Integrase
  • Biochemical Activities and Assays
  • The Integration Reaction
  • References
• Synthesis and Processing of Viral RNA
  AB Rabson and BJ Graves.
  • Transcription
  • Processing of Retroviral RNA
  • Effects of Proviral Integration on Host Gene Expression
  • Concluding Remarks
  • References
• Synthesis, Assembly, and Processing of Viral Proteins
  R Swanstrom and JW Wills.
  • Overview of Retroviral Assembly
  • Synthesis of Gag and Gag-Pro-Pol Proteins
  • Synthesis and Organization of Env Glycoproteins
  • Principles of Particle Assembly
  • Viral RNA Packaging
  • Incorporation of Env into the Viral Particle
  • The Retroviral Protease
  • Maturation of Viral Particles
  • Accessory Proteins and Assembly
  • Summary
  • References
• The Interactions of Retroviruses and their Hosts
  JM Coffin, SH Hughes, and HE Varmus.
  • Retroviral “Lifestyles”: Simple versus Complex
  • Retroviruses and their Interactions with the Host Cell
  • Replication, Differentiation, and the Cell Cycle
  • Effect of Infection on Cell Division and Differentiation
  • Retroviruses and their Interactions with Multicellular Hosts
  • Immune Response to Retroviral Infection
  • Retroviruses as Agents of Genetic Change
  • Conclusion
• Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements
  JD Boeke and JP Stoye.
  • Structural Classes of Retroelements and Replication Strategies
  • Mutational Consequences of Retroelements in the Germ Line
  • Evolution of Retroelements and their Hosts
  • References
• Development and Applications of Retroviral Vectors
  AD Miller.
  • Principles of Retroviral Vector Design
  • Experimental Applications
  • Therapeutic Applications
  • Comparison to Other Gene Transfer Systems
  • Conclusion
  • References
• Retroviral Pathogenesis
  N Rosenberg and P Jolicoeur.
  • Growth and Assay of Pathogenic Retroviruses
  • Oncogenesis
  • Neurological Diseases
  • Retrovirus-Induced Immunodeficiencies
  • Other Retrovirus-Induced Diseases
  • Host Genes that Influence Pathogenesis
  • Transmission and Epidemiology
  • Conclusion
  • References
• Pathogenesis of HIV and SIV
  AS Fauci and RC Desrosiers.
  • Etiologic Agents
  • Cellular Targets of Infection
  • Course of Infection with HIV and SIV
  • Immunopathogenic Mechanisms of HIV Infection
  • Role of Lymphoid Organs in Immunopathogenesis
  • Pathogenesis of Kaposi's Sarcoma and Other Opportunistic Neoplasms
  • Tissue-Specific Disease and Organ System Failure
  • Immune Responses to HIV and SIV
  • Conclusions
  • References
• Immunological and Pharmacological Approaches to the Control of Retroviral Infections
  EA Emini and HY Fan.
  • Immunological Approaches to Controlling Retroviral Infection
  • Pharmacologic Approaches
  • Summary and Perspectives
  • References
• Appendixes
  • Retroviral Sequences
  • Retroviral Taxonomy, Protein Structures, Sequences, and Genetic Maps
  • The Best of Retrotrivia