Virus as Populations

Virus as Populations

Composition, Complexity, Dynamics, and Biological Implications

1st Edition - September 24, 2015

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  • Author: Esteban Domingo
  • Paperback ISBN: 9780128008379
  • eBook ISBN: 9780128009949

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Virus as Populations: Composition, Complexity, Dynamics, and Biological Implications explains fundamental concepts that arise from regarding viruses as complex populations when replicating in infected hosts. Fundamental phenomena in virus behavior, such as adaptation to changing environments, capacity to produce disease, probability to be transmitted or response to treatment, depend on virus population numbers and in the variations of such population numbers. Concepts such as quasispecies dynamics, mutations rates, viral fitness, the effect of bottleneck events, population numbers in virus transmission and disease emergence, new antiviral strategies such as lethal mutagenesis, and extensions of population heterogeneity to nonviral systems are included. These main concepts of the book are framed in recent observations on general virus diversity derived from metagenomic studies, and current views on the origin of viruses and the role of viruses in the evolution of the biosphere.

Key Features

  • Features current views on the key steps in the origin of life and origins of viruses
  • Includes examples relating ancestral features of viruses with their current adaptive capacity
  • Explains complex phenomena in an organized and coherent fashion that is easy to comprehend and enjoyable to read
  • Considers quasispecies as a framework to understand virus adaptability and disease processes


grad students, researchers, med students and investigators in virology, microbiology, and infectious disease; pharmacologists and vaccinologists; theoretical biologists; evolutionary biologists

Table of Contents

    • Foreword
    • Acknowledgments
    • Chapter 1: Introduction to Virus Origins and Their Role in Biological Evolution
      • Abstract
      • 1.1 Considerations on Biological Diversity
      • 1.2 Some Questions of Current Virology and the Scope of This Book
      • 1.3 The Staggering Ubiquity and Diversity of Viruses: Limited Morphotypes
      • 1.4 Origin of Life: A Brief Historical Account and Current Views
      • 1.5 Theories of the Origins of Viruses
      • 1.6 Being Alive Versus Being Part of Life
      • 1.7 Role of Viruses in the Evolution of the Biosphere
      • 1.8 Virus and Disease
      • 1.9 Overview and Concluding Remarks
    • Chapter 2: Molecular Basis of Genetic Variation of Viruses: Error-Prone Replication
      • Abstract
      • 2.1 Universal Need of Genetic Variation
      • 2.2 Molecular Basis of Mutation
      • 2.3 Types and Effects of Mutations
      • 2.4 Inferences on Evolution Drawn from Mutation Types
      • 2.5 Mutation Rates and Frequencies for DNA and RNA Genomes
      • 2.6 Evolutionary Origins, Evolvability, and Consequences of High Mutation Rates: Fidelity Mutants
      • 2.7 Hypermutagenesis and Its Application to Generate Variation: APOBEC and ADAR Activities
      • 2.8 Error-Prone Replication and Maintenance of Genetic Information: Instability of Laboratory Viral Constructs
      • 2.9 Recombination in DNA and RNA Viruses
      • 2.10 Genome Segment Reassortment
      • 2.11 Transition Toward Viral Genome Segmentation: Implications for General Evolution
      • 2.12 Mutation, Recombination, and Reassortment as Individual and Combined Evolutionary Forces
      • 2.13 Overview and Concluding Remarks
    • Chapter 3: Darwinian Principles Acting on Highly Mutable Viruses
      • Abstract
      • 3.1 Theoretical Frameworks to Approach Virus Evolution
      • 3.2 Genetic Variation, Competition, and Selection
      • 3.3 Mutant Distributions During DNA and RNA Virus Infections
      • 3.4 Positive Versus Negative Selection: Two Sides of the Same Coin
      • 3.5 Selection and Random Drift
      • 3.6 Viral Quasispecies
      • 3.7 Sequence Space and State Transitions
      • 3.8 Modulating Effects of Mutant Spectra: Complementation and Interference: An Ensemble as the Unit of Selection
      • 3.9 Viral Populations in Connection with Biological Complexity
      • 3.10 Overview and Concluding Remarks
    • Chapter 4: Interaction of Virus Populations with Their Hosts
      • Abstract
      • 4.1 Contrasting Viral and Host Population Numbers
      • 4.2 Types of Constraints and Evolutionary Trade-Offs in Virus-Host Interactions
      • 4.3 Codon Usage as a Selective Constraint: Virus Attenuation Through Codon and Codon-pair Deoptimization
      • 4.4 Modifications of Host Cell Tropism and Host Range
      • 4.5 Trait Coevolution: Mutual Influences Between Antigenic Variation and Tropism Change
      • 4.6 Escape from Antibody and Cytotoxic T Cell Responses in Viral Persistence: Fitness Cost
      • 4.7 Antigenic Variation in the Absence of Immune Selection
      • 4.8 Constraints as a Demand on Mutation Rate Levels
      • 4.9 Multifunctional Viral Proteins in Interaction with Host Factors: Joker Substitutions
      • 4.10 Alternating Selective Pressures: The Case of Arboviruses
      • 4.11 Overview and Concluding Remarks
    • Chapter 5: Viral Fitness as a Measure of Adaptation
      • Abstract
      • 5.1 Origin of the Fitness Concept and Its Relevance to Viruses
      • 5.2 The Challenge of Fitness In Vivo
      • 5.3 Fitness Landscapes
      • 5.4 Population Factors on Fitness Variations: Collective Fitness and Perturbations by Environmental Heterogeneity
      • 5.5 Quasispecies Memory and Fitness Recovery
      • 5.6 The Relationship Between Fitness and Virulence
      • 5.7 Fitness Landscapes for Survival: The Advantage of the Flattest
      • 5.8 Fitness and Function
      • 5.9 Epidemiological Fitness
      • 5.10 Overview and Concluding Remarks
    • Chapter 6: Virus Population Dynamics Examined with Experimental Model Systems
      • Abstract
      • 6.1 Value of Experimental Evolution
      • 6.2 Experimental Systems in Cell Culture and In Vivo
      • 6.3 Viral Dynamics in Controlled Environments: Alterations of Viral Subpopulations
      • 6.4 Persistent Infections in Cell Culture: Virus-cell Coevolution
      • 6.5 Teachings from Plaque-to-Plaque Transfers
      • 6.6 Limits to Fitness Gain and Loss
      • 6.7 Competitive Exclusion Principle and Red Queen Hypothesis
      • 6.8 Studies with Reconstructed Quasispecies
      • 6.9 Quasispecies Dynamics in Cell Culture and In Vivo
      • 6.10 Overview and Concluding Remarks
    • Chapter 7: Long-Term Virus Evolution in Nature
      • Abstract
      • 7.1 Introduction to the Spread of Viruses. Outbreaks, Epidemics, and Pandemics
      • 7.2 Reproductive Ratio as a Predictor of Epidemic Potential. Indeterminacies in Transmission Events
      • 7.3 Rates of Virus Evolution in Nature
      • 7.4 Long-term Antigenic Diversification of Viruses
      • 7.5 Comparing Viral Genomes. Sequence Alignments and Databases
      • 7.6 Phylogenetic Relationships Among Viruses. Evolutionary Models
      • 7.7 Extinction, Survival, and Emergence of Viral Pathogens. Back to the Mutant Clouds
      • 7.8 Overview and Concluding Remarks
    • Chapter 8: Quasispecies Dynamics in Disease Prevention and Control
      • Abstract
      • 8.1 Medical Interventions as Selective Constraints
      • 8.2 Different Manifestations of Virus Evolution in the Prevention and Treatment of Viral Disease
      • 8.3 Antiviral Vaccines and the Adaptive Potential of Viruses
      • 8.4 Resistance to Antiviral Inhibitors
      • 8.5 Molecular Mechanisms of Antiviral Resistance
      • 8.6 Antiviral Resistance Without Prior Exposure to Antiviral Agents
      • 8.7 Fitness or a Fitness-Associated Trait as a Multidrug-Resistance Mechanism
      • 8.8 Viral Load, Fitness, and Disease Progression
      • 8.9 Limitations of Simplified Reagents and Small Molecules as Antiviral Agents
      • 8.10 “Hit Early, Hit Hard”
      • 8.11 Information and Global Action
      • 8.12 Overview and Concluding Remarks
    • Chapter 9: Trends in Antiviral Strategies
      • Abstract
      • 9.1 The Challenge
      • 9.2 Practiced and Proposed Strategies to Confront the Moving Target Challenge with Antiviral Inhibitors
      • 9.3 Lethal Mutagenesis and the Error Threshold
      • 9.4 Virus Extinction by Mutagenic Agents
      • 9.5 Lethal Mutagenesis In Vivo: Complications Derived From Multiple Mechanisms of Drug Action—The Case of Ribavirin
      • 9.6 Virus Resistance to Mutagenic Agents: Multiple Mechanisms and Evidence of Abortive Escape Pathways
      • 9.7 Virus Extinction as the Outcome of Replacement of Virus Subpopulations: Tempo and Mode of Mutation Acquisition
      • 9.8 The Interplay Between Inhibitors and Mutagenic Agents in Viral Populations: Sequential Versus Combination Treatments
      • 9.9 Prospects for a Clinical Application of Lethal Mutagenesis
      • 9.10 Some Atypical Proposals
      • 9.11 Overview and Concluding Remarks
    • Chapter 10: Collective Population Effects in Nonviral Systems
      • Abstract
      • 10.1 Concept Generalization
      • 10.2 Viruses and Cells: The Genome Size-Mutation-Time Coordinates Revisited
      • 10.3 Darwinian Principles and Intrapopulation Interactions Acting on Cell Populations
      • 10.4 The Dynamics of Unicellular Parasites in the Control of Parasitic Disease
      • 10.5 Cancer Dynamics: Heterogeneity and Group Behavior
      • 10.6 Collective Behavior of Prions
      • 10.7 Molecular Mechanisms of Variation and Clonality in Evolution
      • 10.8 Genomes, Clones, Consortia, Networks, and Power Laws
      • 10.9 An Additional Level of Virus Vulnerability?
      • 10.10 Overview and Concluding Remarks
    • Further Reading
    • Author Index
    • Subject Index

Product details

  • No. of pages: 428
  • Language: English
  • Copyright: © Academic Press 2015
  • Published: September 24, 2015
  • Imprint: Academic Press
  • Paperback ISBN: 9780128008379
  • eBook ISBN: 9780128009949

About the Author

Esteban Domingo

Esteban Domingo
Esteban Domingo studied chemistry and biochemistry at the University of Barcelona, Spain and spent postdoctoral stays at the University of California, Irvine and the University of Zürich. His main interests are the quasispecies structure of RNA viruses and the development of new antiviral strategies. He is presently Professor of Research of the Spanish Research Council (CSIC) at Centro de Biología Molecular "Servero Ochoa" in Madrid.

Affiliations and Expertise

Centro de Biologia Molecular Severo Ochoa, Madrid, Spain

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