Viruses

Molecular Biology, Host Interactions, and Applications to Biotechnology

Paula Tennant, Gustavo Fermin, Jerome E. Foster

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128112571
• eBook ISBN: 9780128111949
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

Viruses: Molecular Biology, Host Interactions, and Applications to Biotechnology provides an up-to-date introduction to human, animal and plant viruses within the context of recent advances in high-throughput sequencing that have demonstrated that viruses are vastly greater and more diverse than previously recognized. It covers discoveries such as the Mimivirus and its virophage which have stimulated new discussions on the definition of viruses, their place in the current view, and their inherent and derived 'interactomics' as defined by the molecules and the processes by which virus gene products interact with themselves and their host's cellular gene products. Further, the book includes perspectives on basic aspects of virology, including the structure of viruses, the organization of their genomes, and basic strategies in replication and expression, emphasizing the diversity and versatility of viruses, how they cause disease and how their hosts react to such disease, and exploring developments in the field of host-microbe interactions in recent years. The book is likely to appeal, and be useful, to a wide audience that includes students, academics and researchers studying the molecular biology and applications of viruses - Provides key insights into recent technological advances, including high-throughput sequencing - Presents viruses not only as formidable foes, but also as entities that can be beneficial to their hosts and humankind that are helping to shape the tree of life - Features exposition on the diversity and versatility of viruses, how they cause disease, and an exploration of virus-host interactions

Chapter 1

Introduction

A Short History of Virology

Gustavo Fermin¹ and Paula Tennant², ¹Universidad de Los Andes, Mérida, Venezuela, ²The University of the West Indies, Mona, Jamaica

Summary

Viruses have played a major role in 20th-century Biology and continue to serve as ideal tools for the dissection of the most intricate life processes. Initially, much of the early studies were focused on deciphering the nature of these unique entities, their interactions with hosts and pathogenesis. Much of what has been learnt proved applicable to understanding of the nature and structure of genes, how genes and genomes operate and how genetic information is replicated over generations. Scientists have since rapidly harnessed the biology of the viruses for the development of new tools and applications in molecular biology, medicine, and agriculture. It is interesting that the very traits employed by viruses to establish infection and induce disease in their hosts are now being manipulated for the production of vectors and biologics that are safe and efficacious. Indeed the convergence of biology, genetics, biochemistry, and physics has propelled the development of molecular biology and advanced the field of Virology, culminating with the realization that viruses are ancient, the most diverse and uncharacterized components of the major ecosystems on Earth, that might also have played a major part in the emergence and consequent structure of modern cellular life.

Keywords

Virus definition; history of virology; filterable agents; viral symbionts; viruses and biotechnology

[Physicists] feel that the field of bacterial viruses is a fine playground for serious children who ask ambitious questions.

Max Delbrück

As masterly expressed by the French microbiologist André Lwoff in his Nobel Lecture of 1965, “For the philosopher, order is the entirety of repetitions manifested, in the form of types or of laws, by perceived objects. Order is an intelligible relation. For the biologist, order is a sequence in space and time. However, according to Plato, all things arise out of their opposites. Order was born of the original disorder, and the long evolution responsible for the present biological order necessarily had to engender disorder. An organism is a molecular society, and biological order is a kind of social order. Social order is opposed to revolution, which is an abrupt change of order, and to anarchy, which is the absence of order. I am presenting here today both revolution and anarchy, for which I am fortunately not the only one responsible. However, anarchy cannot survive and prosper except in an ordered society, and revolution becomes sooner or later the new order. Viruses have not failed to follow the general law. They are strict parasites which, born of disorder, have created a very remarkable new order to ensure their own perpetuation.” In this introductory chapter, we present a short history of the main breakthroughs in the history of virology along with some of the reasons why viruses are considered among the most intriguing and fascinating creations of nature.

C_332,652H_492,388N_98,245O_131,196P_7,501S_2,340

The empirical formula, C_332,652H_492,388N_98,245O_131,196P_7,501S_2,340, represents the chemical composition of the poliovirus, a virus that has earned the reputation of being one of the world’s most feared pathogens. In most infections this virus is limited to the alimentary tract but paralytic poliomyelitis occurs in less than 1% of cases when the virus enters the central nervous system and replicates in the motor neurons of the spinal cord. Describing the poliovirus as a formula portrays the virus as a chemical, a particle of high symmetry containing all the properties required for survival. Even so, one cannot recreate the virus by mixing all its components—even in exact amounts. At most, one could synthesize a template free, biologically meaningful array of logically ordered nucleotides based on prior knowledge—since a virus is more than a chemical entity, and an evolved product of biological information. Indeed viruses were first defined as simple entities, lacking the mechanisms necessary for metabolic function, consisting of a single type of nucleic acid encased in a protein coat. Since some virus particles can form aggregates and bond to each other to form a crystal, viruses were considered as molecular, and not cellular, entities. Many definitions of life, being based on the cellular theory, excluded viruses as living organisms.

The recent discovery of a new group of virus species is, however, challenging the classification of viruses as nonliving entities and has reignited debates on the definition of life. These viruses, designated as mimiviruses, were isolated in 1992 from a water sample collected in an air conditioning system during investigations of a pneumonia outbreak in England. A bacterial etiology was first suspected because of the resemblance to Gram-positive cocci. Electron microscopy in 2003 revealed icosahedral virus particles; the dimensions of which rival those of many microbes. These viruses are three times larger than any virus known at that time and carry DNA genomes consisting of 1.2 million base pairs encoding 1260 genes, 7 of which are common to all cellular life: eukaryotes, bacteria, and archaea. The genome of a relative, a megavirus, was later isolated from a marine sample and shown to be 6.5% larger than that of reported mimiviruses, and unusually packed with DNA repair enzymes. Further analysis of this relative suggested that the complexity of these giant DNA viruses has not yet been uncovered, and perhaps these virus lineages that are as old as those of other microbes on Earth could contribute to the reconstruction of the evolutionary history of viruses. Some researchers are of the view that the giant viruses are the origin of the eukaryotic nucleus; others speculate that they assisted in the emergence of DNA from RNA precursors. These are all hypotheses and much work is needed to understand the origin and evolution of life on Earth.

From Filterable Agent to Genetic Parasite

Much of the initial attention of virologists was focused on viruses as disease causing agents. Certainly, attempts of treating virus infections were recorded long before there was an understanding of the concept of a virus as a distinct entity. Case in point, the development of vaccines and vaccination. Vaccine development began with attempts to prevent infections of the dreaded smallpox disease from as early as the 15th century. In 1796 the Physician Edward Jenner tested his hypothesis that secretions from the wounds that occurred on the udder of milking cows contained material that could protect against smallpox, an acute contagious disease caused by the Variola virus. His hypothesis was based on the observation that milkmaids very rarely contracted the rash that appears on the face and body of an infected person. Instead they often developed pustules on their hands, which were later shown to be caused by the closely related Cowpox virus. A method of intentional infection or variolation was used earlier in China and the Middle East sometime in the 15th and 16th centuries as it was quickly realized that individuals who survived the disease were immune to subsequent infections. The practice involved the application of pustular secretions onto superficial scratches on the arm or leg of an uninfected person, sometimes with grievous consequences and not the mild infection hoped for.

Almost a century later, the French chemist and microbiologist Louis Pasteur, in honoring Jenner’s discovery, coined the term vaccination to refer to the use of a weakened pathogen or “vaccine” to defend against infectious diseases. With the young physician, Emil Roux, Pasteur developed a vaccine against rabies and techniques for attenuating materials he used for his live vaccines. The rabies virus (Rabies lyssavirus) causes acute infection of the central nervous system. In humans the infection is characterized by a neurologic period, coma, and death. By the time the signs of rabies become apparent the disease is nearly always fatal. Pasteur’s vaccine was developed from dried spinal cord tissues collected from rabbits that had died from the infection. The material, initially tested in dogs, was administered to a young boy who had been bitten by a rabid dog and was certain to die. He received multiple shots of the vaccine and survived not only the bite wounds of the attack, but also the experimental vaccine. Pasteur, already a respected scientist, was elevated to the level of an idol—but he never attempted to identify the parasitic agent responsible for the disease. Others after Pasteur, such as Mayer, Ivanovsky, Beijerinck, Loeffler, Frosch, and Reed, showed that infectious agents smaller than bacteria were associated with many of the prevalent diseases at the time. This opened the door to a separate discipline, that of Virology, which came to later contribute to a greater understanding of the most intricate life processes.

Pasteur is also credited for bringing acceptance to the germ theory of disease which states that some diseases are caused by parasitic agents. Prior to the 19th century, disease was thought of as either a divine intervention and punishment or the result of noxious odors. Through Pasteur’s work and the development of microscopic techniques by the German physician and microbiologist Robert Koch, microorganisms became visible and identifiable; and gave credence to the germ theory of disease. In 1840 it was Jacob Henle, Koch’s mentor, who proposed that infectious diseases were caused by living organisms capable of reproducing outside the infected individual. Koch went on to isolate the bacterium responsible for tuberculosis, and from this developed four criteria for the identification of the causative agent of a disease; the pathogen is always associated with a given disease, the pathogen can be isolated from the diseased host and grown in pure culture, the cultured pathogen causes disease when transferred to a healthy susceptible host and the same pathogen is recoverable from the experimentally infected host.

The first evidence that showed the existence of viruses came from experiments set up to fulfill Koch’s postulates and determine the cause of a disease that was plaguing tobacco. In 1879 Adolf Mayer, the director of the Agricultural Experimental Station in Wageningen, Holland, initiated work on tobacco mosaic disease. He reported “the harm done by this disease is often very great and it has caused the cultivation of tobacco to be given up entirely” in the Netherlands and certain parts of Germany. In attempting to follow Koch’s postulates, Mayer used sap extracted from diseased tobacco plants as inoculum to infect healthy tobacco plants. He was successful in reproducing the original disease and subsequently launched a microbiological study to identify the causative agent. Samples were examined microscopically. Samples were passed through filter paper. Samples were cultured on medium devised for growing bacteria. None of these tests were successful in identifying or isolating the etiological agent. Nonetheless, Mayer concluded that the agent was a bacterium that had probably lost activity upon filtration. Dmitri Ivanovsky, a Russian botanist, and the soil microbiologist Martinus Beijerinck, conducted further investigations into the relationship between this etiological agent and the disease of tobacco.

In 1890 Dmitri Ivanovsky was commissioned to study the mosaic disease that was destroying tobacco plants in Crimea. As did Mayer, Ivanovsky showed that sap from diseased tobacco remained infectious to healthy tobacco plants after filtration. Similar observations were obtained when filtrate derived from porcelain filters was used to inoculate healthy tobacco plants. These filters were invented in the 19th and early 20th centuries to retain bacteria and purify water and other liquids. Ivanovsky also reported that it was impossible to grow an organism in pure culture. He came to the conclusion that the pathogenic agent was a minuscule, unculturable bacterium. Beijerinck, on the other hand, proposed a revolutionary idea based on similar observations and three others; the agent could be precipitated by alcohol, it could diffuse through a solid agar medium and it was not able to reproduce outside of a host. Beijerinck then posited that the filterable agent was a unique type of pathogen and coined the term contagium vivum fluidum to convey his concept of a new type of infectious agent that exists in a fluid, noncellular state.

Similar filterable agents too small to be observed by visible light microscopy, but capable of causing disease in animals, were subsequently recognized. Koch’s disciples, Friedrich Loeffler and Paul Frosch (1898), isolated the first agent from animals associated with an extremely contagious disease of cloven footed animals. Later designated the Foot-and-mouth disease virus, the agent that was found filterable, could not be grown on medium used for the cultivation of bacterial pathogens, and it was shown, by dilution, to be infectious. In 1901 Walter Reed and his team isolated the first filterable agent from humans, the Yellow fever virus. Yellow fever is a mosquito-borne viral-spread hemorrhagic fever with a high case–fatality rate. It is endemic to tropical regions of South America and sub-Saharan Africa.

Also around this time a link between filterable or cell-free agents and cancer was proposed. Two Danish scientists in 1908, Vilhelm Ellerman and Oluf Bang, successfully used a cell-free filtrate from chickens with avian erythroblastosis to transmit the disease to healthy chickens. Similarly, 3 years later Peyton Rous in the United States showed that a filterable agent extracted from a sarcoma in chickens was infectious. These findings, however, went unrecognized until interest in the involvement of filterable agents in tumor pathogenesis revived some 20 years later with the discovery of agents responsible for murine tumors. Finally, in 1964, the first filterable agent linked to human cancer was discovered by the United Kingdom scientists Anthony Epstein and Yvonne Barr. The herpesvirus-like Epstein-Barr virus, derived from African Burkitt’s lymphoma tissue. It was years later before it was appreciated that infection is generally not sufficient for cancer, and additional events and host factors, including immunosuppression, somatic mutations, genetic predisposition, and exposure to carcinogens also play a role in the development of cancers.

Concurrently, two independent investigations led to the discovery of filterable agents that infect bacteria, confirming that all organisms can harbor these agents. While trying to grow the bacterium St...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Chapter 1. Introduction: A Short History of Virology
• Chapter 2. Virion Structure, Genome Organization, and Taxonomy of Viruses
• Chapter 3. Replication and Expression Strategies of Viruses
• Chapter 4. Origins and Evolution of Viruses
• Chapter 5. Host Range, Host–Virus Interactions, and Virus Transmission
• Chapter 6. Viruses as Pathogens: Plant Viruses
• Chapter 7. Viruses as Pathogens: Animal Viruses, With Emphasis on Human Viruses
• Chapter 8. Viruses as Pathogens: Animal Viruses Affecting Wild and Domesticated Species
• Chapter 9. Viruses of Prokaryotes, Protozoa, Fungi, and Chromista
• Chapter 10. Host–Virus Interactions: Battles Between Viruses and Their Hosts
• Chapter 11. Beneficial Interactions with Viruses
• Chapter 12. Viruses as Tools of Biotechnology: Therapeutic Agents, Carriers of Therapeutic Agents and Genes, Nanomaterials, and More
• Chapter 13. Viruses as Targets for Biotechnology: Diagnosis and Detection, Transgenesis, and RNAi- and CRISPR/Cas-Engineered Resistance
• Conclusion. It’s a Viral World
• Index