Virus as Populations

Composition, Complexity, Dynamics, and Biological Implications

Esteban Domingo

• Publisher: Academic Press
• Year: 2015
• ISBN:
  9780128009949
• Topic: Scienze biologiche
• Subtopic: Microbiologia e biologia molecolare

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.

• 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

Chapter 1

Introduction to Virus Origins and Their Role in Biological Evolution

Abstract

Viruses are extremely abundant and diverse parasites of cells. They might have arisen during an early phase of the evolution of life on Earth dominated by RNA or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate: viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via lateral transfers of genes. These two models bear on considering viruses predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms.

Keywords

RNA world, Replicon

Virus origins

Microbial evolution

Biosphere

Lateral gene transfer

Chapter Contents

1.1 Considerations on Biological Diversity 2

1.2 Some Questions of Current Virology and the Scope of This Book 3

1.3 The Staggering Ubiquity and Diversity of Viruses: Limited Morphotypes 4

1.4 Origin of Life: A Brief Historical Account and Current Views 8

1.4.1 Early Synthesis of Oligonucleotides: A Possible Ancestral Positive Selection 10

1.4.2 A Primitive RNA World 11

1.4.3 Life from Mistakes, Information from Noninformation: Origin of Replicons 13

1.4.4 Uptake of Energy and a Second Primitive Positive Selection 15

1.5 Theories of the Origins of Viruses 17

1.5.1 Viruses Are Remnants of Primeval Genetic Elements 18

1.5.2 Viruses Are the Result of Regressive Microbial Evolution 19

1.5.3 Viruses Are Liberated Autonomous Entities 20

1.5.4 Viruses Are Elements for Long-Term Coevolution 20

1.5.5 Viruses from Vesicles 21

1.6 Being Alive Versus Being Part of Life 22

1.7 Role of Viruses in the Evolution of the Biosphere 23

1.7.1 Current Exchanges of Genetic Material 24

1.7.2 Symbiotic Relationships 25

1.8 Virus and Disease 25

1.9 Overview and Concluding Remarks 26

References 27

Abbreviations

AIDS acquired immune deficiency syndrome

APOBEC apolipoprotein B mRNA editing complex

CCMV cowpea chlorotic mottle virus

dsRNA double stranded RNA

E. coli Escherichia coli

eHBVs endogenous hepatitis B viruses

HBV hepatitis B virus

HCV hepatitis C virus

HDV hepatitis delta virus

HIV-1 human immunodeficiency virus type 1

ICTV International Committee on Taxonomy of Viruses

Kbp thousand base pairs

mRNA messenger RNA

PMWS postweaning multisystemic wasting syndrome

RT reverse transcriptase

RdRp RNA-dependent RNA polymerase

ssRNA single stranded RNA

T7 bacteriophage T7

tRNA transfer RNA

UV ultraviolet

1.1 Considerations on Biological Diversity

To approach the behavior of viruses acting as populations, we must first examine the diversity of the present-day biosphere, and the physical and biological context in which primitive viral forms might have arisen. Evolution pervades nature. Thanks to new theories and to the availability of powerful instruments and experimental procedures, which together constitute the very roots of scientific progress, we are aware that the physical and biological worlds are evolving constantly. Several classes of energy have gradually shaped matter and living entities, basically as the outcome of random events and Darwinian natural selection in its broadest sense. The identification of DNA as the genetic material, and the advent of genomics in the second half of the twentieth century unveiled an astonishing degree of diversity within the living world that derives mainly from combinations of four classes of nucleotides. Biodiversity, a term coined by O. Wilson in 1984, is a feature of all living beings, be multicellular differentiated organisms, single cell organisms, or subcellular genetic elements, among them the viruses. Next generation sequencing methods developed at the beginning of the twenty-first century, which allow thousands of sequences from the same biological sample (a microbial community, a tumor, or a viral population) to be determined, has further documented the presence of myriads of variants in a “single biological entity” or in “communities of biological entities.” Differences extend to individuals that belong to the same biological group, be it Homo sapiens, Droshophila melanogaster, Escherichia coli, or human immunodeficiency virus type 1 (HIV-1). No exceptions have been described.

During decades, in the first half of the twentieth century, population genetics had as one of its tenets that genetic variation due to mutation had for the most part been originated in a remote past. It was generally thought that the present-day diversity was essentially brought about by the reassortment of chromosomes during sexual reproduction. This view was weakened by the discovery of extensive genetic polymorphisms, first in Drosophila and humans, through indirect analyses of electrophoretic mobility of enzymes, detected by in situ activity assays to yield zymograms that were displayed as electromorphs. These early studies on allozymes were soon extended to other organisms. Assuming that no protein modifications had occurred specifically in some individuals, the results suggested the presence of several different (allelic) forms of a given gene among individuals of the same species, be humans, insects, or bacteria. In the absence of information on DNA nucleotide sequences, the first estimates of heterogeneity from the numbers of electromorphs were collated with the protein sequence information available. An excellent review of these developments (Selander, 1976) ended with the following premonitory sentence on the role of molecular biology in unveiling evolutionarily relevant information: “Considering the magnitude of this effect, we may not be overfanciful to think that future historians will see molecular biology more as the salvation for than, as it first seemed, the nemesis of evolutionary biology.”

The conceptual break was confirmed and accentuated when molecular cloning and nucleotide sequencing techniques produced genomic nucleotide sequences from multiple individuals of the same biological species. Variety has shaken our classification schemes, opening a debate on how to define and delimit biological “species” in the microbial world. From a medical perspective it has opened the way to “personalized” medicine, so different are the individual contexts in which disease processes (infectious or other) unfold. Diversity is a general feature of the biological world, with multiple implications for interactions in the environment, and also for human health and disease (Bernstein, 2014).

1.2 Some Questions of Current Virology and the Scope of This Book

Viruses (from the Latin “virus,” poison) are no exception regarding diversity. The number of different viruses and their dissimilarity in shape and behavior is astounding. Current estimates indicate that the total number of virus particles in our biosphere reaches 10³², exceeding by one order of magnitude the total number of cells. Viruses are found in surface and deep sea and lake waters, below the Earth surface, in any type of soil, in deserts, and in most environments designated as extreme regarding ionic conditions and temperature (Breitbart et al., 2004; Villarreal, 2005; Lopez-Bueno et al., 2009; Box 1.1). The viruses that have been studied are probably a minimal and biased representation of those that exist, with at least hundred thousands mammalian viruses awaiting discovery, according to some surveys (Anthony et al., 2013). This is because high-throughput screening procedures have only recently become available, and also because prevention of disease has provided the main incentive to study viruses. Disease-associated viruses are those most described in the scientific literature.

Box 1.1

Some Numbers Concerning Viruses in the Earth Biosphere

• Total number of viral particles: ~ 10³². This is 10 times more than cells, and they are equivalent to 2 × 10⁸ tons of carbon.

• Virus particles in 1 cm³ of sea water: ~ 10⁸.

• Virus particles in 1 m³ of air: ~ 2 × 10⁶ to 40 × 10⁶.

• Rate of viral infections in the oceans: ~ 1 × 10²³/s.

• A string with the viruses on Earth would be about ~ 2 × 10⁸ light years long (~ 1.9 × 10²⁴ m). This is the distance from Earth of the galaxy clusters Centaurus, Hydra, and Virgo.

Based on: Suttle (2007), Whon et al. (2012), and Koonin and Dolja (2013).

Current virology poses some general and fascinating questions which are not easily approachable experimentally. Here are some:

• What is the origin of viruses?

• What selective forces have maintained multiple viruses as parasites of unicellular and multicellular organisms? Why a few viral forms have not outcompeted most other forms? Or have they?

• What has been the role, if any, of viruses in our biosphere?

• Have they played essential evolutionary roles, and do such roles continue at the present time? Are viruses mere selfish, perturbing entities?

• Have viruses been maintained as modulators of the population numbers of their host species?

• Does virus variation play a role in the unfolding of viral disease processes?

• Is the behavior of present-day viruses at the population level an inherit...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Foreword
• Acknowledgments
• Chapter 1: Introduction to Virus Origins and Their Role in Biological Evolution
• Chapter 2: Molecular Basis of Genetic Variation of Viruses: Error-Prone Replication
• Chapter 3: Darwinian Principles Acting on Highly Mutable Viruses
• Chapter 4: Interaction of Virus Populations with Their Hosts
• Chapter 5: Viral Fitness as a Measure of Adaptation
• Chapter 6: Virus Population Dynamics Examined with Experimental Model Systems
• Chapter 7: Long-Term Virus Evolution in Nature
• Chapter 8: Quasispecies Dynamics in Disease Prevention and Control
• Chapter 9: Trends in Antiviral Strategies
• Chapter 10: Collective Population Effects in Nonviral Systems
• Further Reading
• Author Index
• Subject Index