Virus As Populations: Composition, Complexity, Quasispecies, Dynamics, and Biological Implications

Cover
Virus as Populations
Copyright
Foreword
Preface for the second edition
Acknowledgments
1 -
Introduction to virus origins and their role in biological evolution
	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
		1.4.1 Early synthesis of oligonucleotides: a possible ancestral positive selection
		1.4.2 A primitive RNA world
		1.4.3 Life from mistakes, information from noninformation: origin of replicons
		1.4.4 Uptake of energy and a second primitive positive selection
		1.4.5 Definitions of life
	1.5 Theories of the origins of viruses
		1.5.1 Viruses are remnants of primeval genetic elements
		1.5.2 Viruses are the result of regressive microbial evolution
		1.5.3 Viruses are liberated autonomous entities
		1.5.4 Viruses are elements for long-term coevolution
		1.5.5 Viruses from vesicles
	1.6 Teachings from mycoviruses
	1.7 Being alive versus being part of life
		1.7.1 Role of viruses in the evolution of the biosphere
		1.7.2 Current exchanges of genetic material
		1.7.3 Symbiotic relationships
	1.8 Virus and disease
	1.9 Viral and cellular dynamics and the tree of life
	1.10 Overview and concluding remarks
	References
2 -
Molecular basis of genetic variation of viruses: error-prone replication
	2.1 Universal need for 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
		2.5.1 Undesired consequences of the confusion between mutation rates and mutation frequencies
	2.6 Evolutionary origins, evolvability, and consequences of high mutation rates: fidelity mutants
	2.7 Hypermutagenesis and its application to generating a 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
		2.9.1 Molecular occurrence versus observed recombination
	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
		2.12.1 Mechanistically unavoidable versus evolutionarily relevant genetic variation
	2.13 Overview and concluding remarks
	References
3 -
Darwinian principles acting on highly mutable viruses
	3.1 Theoretical frameworks to approach virus evolution
		3.1.1 Theory and experiment
	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
		3.6.1 The origins of quasispecies theory
		3.6.2 Deterministic versus stochastic quasispecies
		3.6.3 Mutant spectra, master genomes, and consensus sequences
		3.6.4 Measurement of quasispecies complexity
			3.6.4.1 Mutant spectrum depth and dynamics
			3.6.4.2 Diversity indices
		3.6.5 Some key points on the impact of quasispecies in virology
	3.7 Sequence space and state transitions
		3.7.1 Virus evolution as a movement in sequence space
		3.7.2 Exploration of sequence space and the sampling problem: viral population size as a key parameter
	3.8 Modulating effects of mutant spectra: interference, cooperation and complementation. An ensemble as the unit of selection
		3.8.1 Molecular mechanisms of complementation and interference
		3.8.2 Individual versus group selection
		3.8.3 Stochastic effects in selected collectivities
	3.9 Viral populations in connection with biological complexity
	3.10 Overview and concluding remarks
	References
4 -
Interaction of virus populations with their hosts
	4.1 Contrasting viral and host population numbers
		4.1.1 Productive power of some viral infections
		4.1.2 Population size limitations and the effect of bottlenecks: the effective population size
	4.2 Types of constraints and evolutionary trade-offs in virus-host interactions
		4.2.1 Long-term history dictates basal constraints
		4.2.2 Cell-dependent constraints: No free lunch
		4.2.3 Constraints in host organisms: contrast with man-made antiviral interventions
	4.3 Codon usage as a selective constraint: virus attenuation through codon and codon-pair deoptimization
		4.3.1 The synonymous codon space can affect an evolutionary outcome
	4.4 Modifications of host cell tropism and host range
		4.4.1 Nonstructural viral proteins and RNA in cell tropism and host range of viruses
	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
		4.10.1 The sophistication of pathogen-vector-host interactions in plant viruses
	4.11 Overview and concluding remarks
	References
5 -
Viral fitness as a measure of adaptation
	5.1 Origin of the fitness concept and its relevance to viruses
		5.1.1 Measurement of viral fitness
		5.1.2 Power and limitations of fitness measurements
		5.1.3 Dissection of fitness determinants
	5.2 The challenge of fitness in vivo
	5.3 Fitness landscapes
		5.3.1 Justification of ruggedness in fitness landscapes for viruses
	5.4 Population factors on fitness variations: collective fitness and perturbations by environmental heterogeneity
	5.5 Quasispecies memory and fitness recovery
		5.5.1 Implications of quasispecies memory: harbinger mutations
	5.6 The relationship between fitness and virulence
	5.7 Fitness landscapes for survival: the advantage of the flattest
	5.8 Fitness and function
		5.8.1 Very low fitness versus lethality
	5.9 Epidemiological fitness
	5.10 Overview and concluding remarks
	References
6 -
Virus population dynamics examined with experimental model systems
	6.1 Value of experimental evolution
	6.2 Experimental systems in cell culture and in vivo
		6.2.1 “To culture is to disturb”
		6.2.2 Experimental evolution in vivo
	6.3 Viral dynamics in controlled environments: alterations of viral subpopulations
	6.4 Persistent infections in cell culture: virus-cell coevolution
		6.4.1 Back again 4000 million years: contingency in evolution
	6.5 Teachings from plaque-to-plaque transfers
		6.5.1 Muller’s ratchet and the advantage of sex
		6.5.2 Molecular basis of fitness decrease: deep fluctuations, massive extinctions, and rare survivors
	6.6 Limits to fitness gain and loss
	6.7 Competitive exclusion principle and Red Queen hypothesis
		6.7.1 Contingent neutrality in virus
	6.8 Studies with reconstructed quasispecies
	6.9 Quasispecies dynamics in cell culture and in vivo
	6.10 Overview and concluding remarks
	References
7 -
Long-term virus evolution in nature
	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
		7.3.1 Influence of the time of sampling
		7.3.2 Interhost versus intrahost rate of evolution
		7.3.3 Rate discrepancies and the clock hypothesis
	7.4 Long-term antigenic diversification of viruses
		7.4.1 Widely different number of serotypes among genetically variable viruses
		7.4.2 Similar frequencies of monoclonal antibody-escape mutants in viruses differing in antigenic diversity
	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
		7.7.1 Factors in viral emergence
		7.7.2 Complexity revisited
	7.8 Overview and concluding remarks
	References
8 -
Quasispecies dynamics in disease prevention and control
	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
		8.3.1 Some requirements for the design of vaccines to control highly variable viruses
		8.3.2 Vaccination-induced evolution
	8.4 Resistance to antiviral inhibitors
		8.4.1 Replicative load and antiviral resistance
		8.4.2 Barriers to drug resistance
		8.4.3 Drug efficacy, mutant frequencies, and selection of escape mutants
		8.4.4 Phenotypic barrier and selective strength
		8.4.5 Multiple pathways and evolutionary history in the acquisition of drug resistance
	8.5 Molecular mechanisms of antiviral resistance
		8.5.1 Some examples with HIV-1
		8.5.2 Mutation site and functional barrier
		8.5.3 Additional considerations on escape mutant frequencies
	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
	References
9 -
Trends in antiviral strategies
	9.1 The challenge
		9.1.1 Virus as moving targets
	9.2 Practiced and proposed strategies to confront the moving target challenge with antiviral inhibitors
		9.2.1 Combination treatments
		9.2.2 Split treatments
		9.2.3 Targeting cellular functions
		9.2.4 Use of drugs that stimulate the host innate immune system
		9.2.5 Combined use of immunotherapy and chemotherapy
	9.3 Lethal mutagenesis and the error threshold
		9.3.1 Reconciliation of theory and experiment: a proposal
	9.4 Virus extinction by mutagenic agents
		9.4.1 The search for new mutagenic nucleotide analogs
	9.5 Lethal mutagenesis in vivo: complications derived from multiple mechanisms of drug action—the case of ribavirin
		9.5.1 Favipiravir as antiviral inhibitor and mutagen
	9.6 Virus resistance to mutagenic agents: multiple mechanisms and evidence of abortive escape pathways
		9.6.1 Unpredictable effects of some polymerase substitutions
		9.6.2 Polymerase fidelity and modulation of nucleotide incorporation
	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
	References
10 -
Collective population effects in nonviral systems
	10.1 Concept generalization
	10.2 Viruses and cells: the genome size-mutation-time coordinates revisited
		10.2.1 A comparison of antiviral and antibiotic resistance
	10.3 Darwinian principles and intrapopulation interactions acting on bacterial cell populations
	10.4 The dynamics of unicellular parasites in the control of parasitic disease
	10.5 Cancer dynamics: heterogeneity and group behavior
		10.5.1 The two-component theory of cancer: similarities with other biological systems, and therapeutic implications
	10.6 Collective behavior of prions
	10.7 Molecular mechanisms of variation and clonality in evolution
	10.8 Genomes, clones, consortia, and networks
		10.8.1 Interacting networks and power laws
	10.9 An additional level of virus vulnerability?
	10.10 Overview and concluding remarks
	References
Subject Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	Y
	Z
Author Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Y
	Z
Back Cover