VIRUSPHERE EB

Frank Ryan

• Publisher: William Collins
• Year: 2019
• Print ISBN: 9780008296704
• eBook ISBN: 9780008296698
• Topic: Biological Sciences
• Subtopic: Diseases & Allergies
• Index: Biological Sciences

A virologist's insight into how viruses evolve and why global epidemics are inevitable

In 1993 a previously healthy young man was drowning in the middle of a desert, in fluids produced by his own lungs. This was the beginning of the terrifying Sin Nombre hantavirus epidemic and the start of a scientific journey that would forever change our understanding of what it means to be human.

After witnessing the Sin Nombre outbreak, Dr Frank Ryan began researching viral evolution and was astonished to discover that it's inextricable from the evolution of all life on Earth. From AIDS and Ebola to the common cold, Ryan explores the role of the virus within every ecosystem on the planet. His gripping conclusions shed new light on the natural world, proving that what doesn't kill you really does make you (and your species) stronger.

I

What Are Viruses?

Only in the last decade have we come to realise that, from its very beginnings, all of cellular life has inhabited not only the visible biosphere – of solid earth, air and oceans – but also a less familiar and invisible virosphere. The viruses that constitute this virosphere are not merely surrounding us, they are within us, both as evolving extrinsic organisms in themselves and as interactive symbiotic entities that are an intrinsic part of our being. We might not be aware of the presence of these minuscule passengers within us from moment to moment, but the passengers are, in their quintessentially viral way, aware of us.

This might seem somewhat daunting, even frightening, to some of us, but there is no need for alarm. They have always been there. It is likely that they preceded any origins of human life on planet Earth, or indeed, going further back, the origins of the mammals, or any animals or plants, or fungi, or, if I am right, even the single-celled amoebae. All that has changed is that the world of virology is coming to understand the role of viruses in the origins and diversity of life, and what might appear incongruous to any notion of viruses being exclusively agents of disease, the health of the biosphere.

For viruses to achieve all this they must surely possess some remarkable properties. For example, they have no means of locomotion yet they move among us: in pandemic forms they effortlessly circulate around the globe. Although they have no sense of vision, hearing, touch, smell or taste, they detect with uncanny precision the cell, or organ or tissue that is their target destination. This they achieve despite the relentless opposition of powerful immune defences designed to prevent this happening; and once arrived, they penetrate the defences of the target cell, break entry through its protective surface membrane, and once inside take over its physiological, biochemical and genetic programming to compel the cell to become a factory for the production of a new generation of themselves.

Welcome to the world of viruses!

It is, admittedly, a very strange world replete with mysteries. It becomes all the more quixotic when we attempt to examine it at the most basic level.

What then are viruses? How do we even begin to define them? What, for instance, is the difference between, say, a bacterium and a virus? While viruses and bacteria are often confused in the minds of ordinary folk, because they cause many of the common infectious diseases, bacteria and viruses are very different entities. Viruses are more difficult to define than bacteria because they are said to occupy a position somewhere between the biological notions of life and non-living chemicals. This has tempted a distinguished colleague to dismiss them as ‘a piece of mischief wrapped up in a protein’. While the hubris contains a grain of truth, there is rather more to viruses than being merely a source of mischief. So let us delve a little deeper! Do viruses rely on genes, and genomes, like all of the more familiar forms of life, from whales to humans and buttercups to the so-called ‘humble’ bacterium? The answer to that question is, ‘Yes!’ Viruses do indeed have genomes, which contain protein-coding genes. We shall discover more about those viral genomes in subsequent chapters when we shall also observe some important differences between the genomes of viruses and all other organisms.

Do viruses follow the same patterns of evolution as, say, plants and animals? The answer again is, ‘Yes!’ But the patterns of evolution – the specific mechanisms involved – are heavily influenced by a facet of their organismal existence that is confined to viruses. Viruses can only replicate by making use of the host cell’s genetic apparatus, and because of this, viruses were formerly defined as ‘obligate genetic parasites’. But with our increasing understanding of viruses, and of their complex roles in relation to the evolution of their hosts, this definition is no longer sufficient to characterise them. A more adequate definition must take on board the fact that viruses are symbionts. Indeed, we now know that viruses are the ultimate symbionts, exhibiting many examples of all three patterns of symbiotic behaviour, namely parasitism, commensalism and mutualism. Moreover, since viruses will sometimes employ aggression as an evolutionary pattern of behaviour in relation to their hosts, they are also potentially ‘aggressive symbionts’.

The more we examine viruses, in their evolutionary trajectories and in the influence of that trajectory on the evolution of their hosts, the stranger and more fascinating their story becomes. Is it reasonable to propose that viruses were born at the stage of chemical self-replicators before the actual advent of cellular life on Earth? If so, how then, from those primal beginnings, did viruses evolve, to interact with, and thus contribute to, the evolution of all of life on this planet?

The aim of this book will be to enlighten readers through a step-wise progression, starting with a familiar territory: we shall confront the wide range of illnesses that are caused by viruses. For example, we shall examine what is really going on in the common cold, the childhood illnesses such as measles, chickenpox, herpes and mumps, rubella, as well as less familiar examples such as rabies, ‘breakbone fever’, haemorrhagic fevers such as Ebola, and virus-induced cancers such as Burkitt’s lymphoma. In such an examination we shall discover what makes viruses tick, exploring what’s actually going on inside us when we encounter the virus, how this gives rise to the symptoms we get from the infection, and, key to deeper understanding, probing what the virus itself gets from the ‘interaction’ with its human host. We shall employ the same virus-orientated perspective to explore important epidemic forms such as influenza, smallpox, AIDS and polio, which will illustrate how viral infections have impacted on human social history, from the wall paintings of the Ancient Egyptians to the colonisations of the Americas, Australasia and Africa. We shall also take a close look at vaccines as a measure to prevent epidemic infections, from the first introduction of vaccination against smallpox centuries ago to the recent controversy concerning the triple vaccine and the papilloma virus vaccine.

The science of virology grew out of the study of viruses in the causation of disease. Through understanding the viruses already familiar to us, we shall widen our enlightenment by examining the role of viruses in the evolution of life, and in particular we shall explore the role of viruses in our human evolutionary history. We shall see how, throughout our prior evolution, we have shared our existence with these powerful invisible entities, and how they really have changed us at the most intimate level, to help make us human.

I hope that, like me, you will come to appreciate the enormous importance of viruses to life, in its origins and complexity, while also marvelling at the existential nature of what is one of the great wonders of life on our beautiful blue-oceanic planet. Viruses, by and large, have had a bad press. This is understandable, given the experiences of earlier generations of virologists, whose only contact with viruses was in dealing with the infections caused by them. But today a major wind of change is blowing through the world of virology – so much so that recently a distinguished evolutionary virologist declared that we were witnessing what he called ‘The Great Virus Comeback’. What does he mean by this? Why have some of the modern pioneers of virology introduced the term ‘virosphere’ as the key to a new exploration of the importance of viruses to the entire biosphere? Could it be true that, as some would have us believe, viruses should now be seen as the ‘Fourth Domain of Life’?

2

Coughs and Sneezes Spread Diseases

Historically, viruses were included with the so-called ‘microbes’ – tiny organisms that were originally discovered as the cause of infectious diseases in humans, animals and plants. Interestingly, there is a part of us that has long been intimately acquainted with microbes in general, and with viruses in particular. This is our inbuilt system of defences against infection: what doctors refer to as our immune system. It is perhaps as well that we possess this inbuilt immunological protection, because we inhabit a world that teems with microbes.

A veritable zoo of such microbes covers our skin and other surface membranes. Biologists call this the ‘human microbiome’. Although it might cause some of us to squirm a little just to acknowledge its existence, this secret world is no real threat to us. It is an intrinsic part of our being, comprising a variety of bacteria, as well as other microbial forms, that inhabit our surface skin, mouth and throat, nostrils and nasal cavities, and in the case of women, the genital passages. Our bodies are said to contain roughly 30 to 40 trillion cells – if you are mathematically inclined, this is 3 to 4 times 10¹³ – which comprises the sum total of living cells that make up our living tissues and organs. Meanwhile our ‘microbiome’, which amounts to all of the microbes that inhabit our skin, gut, oral and nasal passages and throat, and genital tract in women, accounts for some ten times as many microbial cells, comprising such organisms as bacteria, Archaea and protists. It is natural enough, given our awareness of past epidemics and day-to-day troublesome infections, to assume that such microbes are invariably harmful; but these microbes that make up our personal microbiomes are not hostile. Some simply live off us in commensal fashion without causing us any harm; while many others help to maintain our normal health. For example, the zoo of microbes that inhabit our large bowels, or colons, play an important beneficial role in our human nutrition – such as in helping us to absorb vitamin B12 – as well as helping to protect us from invasion of our digestive tract by pathological visitors. The bodies of this ‘colonic flora’ account for no less than 30 per cent of the bulk of our faecal waste.

There is also growing evidence that we benefit in a number of other ways from this microbial flora of our skin, and other abdominal cavities. This holistic realisation begs a relevant question: could viruses be a part of this human biome, capable of contributing to our human health? For any group of microbes to contribute to the nutrition or general well-being of a host, this would imply a lengthy period of symbiotic evolution with the same host. Immediately we even come to consider such a curious virus–host interaction, we are obliged to consider something profoundly different about viruses when compared to cellular symbionts, such as the bacterial flora of the human intestine or skin. Viruses inhabit the landscape of the host genome.

This means that viruses are certainly not going to contribute, for example, to human vitamin digestion. What it really implies is that, if viruses are to contribute in some way to host health – or indeed host evolution – that contribution is likely to be much more subtle, involving, perhaps in the human host, an interaction with our immunological defences, or more profoundly still, an interaction with our human genetic machinery – or most profound of all, changing our very human genome, the repository of our human heredity, buried deep in the nucleus of every human cell. If this were to happen, viruses would have contributed to what makes us human.

These are weighty questions. Perhaps many of my readers might be inclined to make the point that, so far as they are aware, only the less helpful kinds of viruses appear to have come their way.

In this book we shall explore the truly strange, and intriguing, world of viruses. We might make a start by dispelling a common misconception; many people tend to confuse viruses with bacteria. This is perfectly understandable since viruses, like bacteria, cause many of the common ailments that afflict us in our ordinary lives, and particularly so the fevers that beset the lives of our children. Family doctors deal with these common ailments on a day-to-day basis, and they tend to treat them in similar ways, with antibiotics for bacterial illnesses and vaccination programmes or antiviral drugs aimed at protecting kids from the common viral infections. It is little wonder that people are apt to confuse viruses with bacteria. What then is the difference between the two?

In fact there are major differences between bacteria and viruses. The most obvious difference is one of scale: most viruses are much smaller than bacteria. We readily grasp this if we take a closer look at what is going on during those coughs and sneezes that we recognise as the harbingers of that bothersome cold. While a few other viruses can cause an illness resembling a cold, the majority of colds are caused by a particular virus, which goes by the name of ‘rhinovirus’. If one harks back to the sneezing, snuffling and nose-blowing that are the familiar symptoms of that developing cold, the name rhinovirus is apt, since ‘rhino’ derives from the Greek word, rhinos, for nose. Rhinoviruses are the commonest virus infections to afflict humans worldwide, with a seasonal peak in the autumn and early winter. The more we learn about the rhinovirus, the more we witness how well-suited it is to its natural environment, and to its life cycle of infectious behaviour and spread.

The rhinovirus is exceedingly tiny, at about 18 to 30 nanometres in diameter. A nanometre, or nm, is one-thousand-millionth of a metre. This clearly tells us that a single rhinovirus organism – it is referred to as a ‘virion’ – is absolutely minuscule. In the evolutionary system of classification known as ‘taxonomy’, rhinoviruses are classed as a genus within the family of the ‘picornaviruses’, a word derived from pico for small, and rna, because the rhinovirus genome is made up of the nucleic acid RNA rather than the more familiar DNA. Let us put aside any discussion of these genetic molecules for the moment, but we shall return to consider some remarkable implications of RNA-based viral genomes in subsequent chapters.

Returning to the differences in scale between viruses and bacteria, rhinoviruses are far too small to be seen under the ordinary laboratory light microscope. The virions can only be visualised under the phenomenal magnification of the electron microscope, when they appear to be roughly spherical in shape, resembling tiny balls of wool. In fact, if we examine the individual virions more closely under the electron microscope, we see that they are not really spheres but have multifaceted surfaces, rather like cut diamonds. In the technical jargon, the multifaceted surface of the rhinovirus is the viral ‘capsid’, which is the viral equivalent of a human cell’s enclosing membrane. This capsid has a striking mathematical symmetry comprising 20 equilateral triangles. All viruses have genomes, made up of either DNA or its sister molecule, RNA. The protein capsid acts as a protective shell that encloses the viral genome. It is the capsid that gives rhinoviruses their quasi-crystalline appearance, known as ‘icosahedral’ symmetry – the term is simply the Greek for ‘twenty-sided’. The multifaceted symmetry is not comprised of diamantine crystal, however, but constructed by a biochemical protein assembly.

Microbiologists had long recognised the presence of viruses before the electron microscope was invented. They found ways of detecting the presence of viruses from their effects on host cells, and they could even count their precise numbers from their cytopathic effects in cultures. It will come as no surprise to discover that the best cultures for growing rhinoviruses are cells derived from the human nasal lining, or the lining of the windpipe, or trachea. We are equally unsurprised to learn that the best temperature at which to culture cold viruses is between 33°C and 35°C, which is the temperature found within our human nostrils on a cold autumnal or winter’s day.

Rhinoviruses are highly adapted for survival in their host environment. They are also highly adapted to infect a specific host. This became apparent when scientists attempted to infect laboratory animals, including chimpanzees and gibbons, with a variety of different subtypes of rhinovirus that readily infected humans. They could not replicate the symptoms of a typical cold in any of the animals. From this we glean an important lesson about viruses: the rhinovirus is most particular when it comes to its choice of host, which is exclusively Homo sapiens. This has a pertinent significance; it means that human infection is vitally important to virus survival. Only through human to human contagion can the virus be passed on and breed new generations of rhinovirus. We are the natural reservoir of the cold virus.

But a moment or two of reflection on such exclusivity provokes a tangential thought – and a pertinent question. These minuscule polyhedral balls have no obvious means of locomotion. How can they possibly move about through our human population to effortlessly spread their infection across national and even international boundaries?

In fact, we already have the answer: it is implied in the very title of this chapter. Why do we cough and sneeze? We do so because this is what happens when our noses, throats and windpipe passages feel irritated. It is part of the natural defences against foreign material entering passages where it could block our airways and, implicitly, obstruct them and threaten our breathing. What rhinoviruses do is to provoke the same physiological responses by irritating the linings of our nasal passages. The viruses spread from person to person because they are explosively ejected into the ambient air with every cough and sneeze, to be inhaled and subsequently infect new hosts. And here, once again, we learn something vitally important about viruses. The viruses do not need any mechanism of locomotion because they hitch a ride on our own locomotion, and everywhere we go, we further oblige them by spreading their contagion by coughing and sneezing.

How clever, we are inclined to think, are viruses!

But viruses could not possibly be clever. They are far too simple to be capable of thinking for themselves. We are instead confronted by another of the numerous enigmas in relation to viruses. How, for example, could an organism some paltry 30 nanometres in diameter acquire such devious but also such highly effective patterns of behaviour as we discover in the common cold? The answer is that viruses do this through their evolution. Indeed, viruses have an extraordinary capacity to evolve. They evolve much faster than humans, even much faster than bacteria. Over subsequent chapters we shall see how that viral employment of host locomotion is one of many such evolutionary adaptations.

What then do rhinoviruses do when they get inside us?

We have seen that the rhinovirus has a specific target cell, the cilia-flapping cells lining the nasal passages. Once inhaled, the virus targets these lining cells, discovering a specific ‘receptor’ in the cell’s surface membrane, after which the virus uses the receptor to break through the membranous barrier and gain entry into the cell’s interior, or cytoplasm. Here the virus hijacks the cell’s metabolic pathways to convert it into a factory for the replication of daughter viruses. The daughter viruses are extruded into the nasal and air passages, there to search out new cells to infect and continue the invasive process. It seems to require only a tiny dose of virus to be inhaled from the expelled cough or sneeze of an infected person to initiate infection in a new individual. After arrival, the incubation period from virus entry to infected nasal cells exuding new daughter viruses can be as little as a day. We don’t have much of a chance of escaping infection once the virus has been inhaled. Virus replication peaks by day four.

Fortunately, it isn’t all one way. Even as the virus is launching its attack, the human immune system has registered the threat, and it has recognised the viral antigenic signature – what we call the serotype. The problem is that the arrival of a new serotype requires time for the immune system to recognise the threat and to build up a formidable arsenal of responses. By day...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Epigraph
• Contents
• Introduction
• 1. What Are Viruses?
• 2. Coughs and Sneezes Spread Diseases
• 3. A Plague Upon a Plague
• 4. Every Parent’s Nightmare
• 5. A Bug Versus a Virus
• 6. A Coincidental Paralysis
• 7. Deadly Viruses
• 8. An All-American Plague
• 9. Lurker Viruses
• 10. How Flu Viruses Reinvent Themselves
• 11. A Lesson from a Machiavellian Virus
• 12. The Mystery of Ebola
• 13. The Mercurial Nature of the Zika Virus
• 14. A Taste for the Liver
• 15. Warts and All
• 16. Lilliputian Giants
• 17. Are Viruses Alive?
• 18. Inspiring Terror – and Delight
• 19. The Ecology of the Oceans
• 20. The Virosphere
• 21. The Origins of the Placental Mammals
• 22. Viruses in the Origins of Life
• 23. The Fourth Domain?
• Bibliography and References
• Index
• About the Book
• About the Author
• Also by Frank Ryan
• About the Publisher