Principles of Molecular Virology (eBook)

Alan J. Cann (Autor)

eBook Download: PDF | EPUB

2015 | 6. Auflage
318 Seiten
Elsevier Science (Verlag)
978-0-12-801955-9 (ISBN)

Infos

Principles of Molecular Virology, Sixth Edition, provides an easily accessible introduction to modern virology, presenting principles in a clear and concise manner. This fully updated edition explores and explains the fundamental aspects of virology, including the structure of virus particles and genome, replication, gene expression, infection, pathogenesis and subviral agents. In addition, this update reflects advances made in the field, including HIV pathogenesis, cryoelectron microscopy, bioinformatics, and RNA interference. - Provides a conceptual approach to the principles of molecular virology, with important examples of new advances in virology - Includes online resources for students and instructors - New concepts in this edition include coverage of newly discovered and emergent viruses such as MERS and Ebola - Presents new and updated information on bioinformatics and metagenomics - Contains updated learning outcomes and further reading for each chapter

Dr. Alan J. Cann has worked in both the U.K. and U.S.A. teaching undergraduate, postgraduate, and medical students. He is currently a Senior Lecturer in Biological Sciences at the University of Leicester where his research interests include pedagogic research and science communication.

Inhalt

Front Cover 1
Principles of Molecular Virology 4
Copyright Page 5
Contents 6
Preface to the Sixth Edition 10
1 Introduction 12
What Are Viruses? 13
Are Viruses Alive? 14
The History of Virology 15
Living Host Systems 17
Cell Culture Methods 19
Serological/Immunological Methods 20
Ultrastructural Studies 24
Molecular Biology 29
Further Reading 35
2 Particles 38
The Function and Formation of Virus Particles 38
Capsid Symmetry and Virus Architecture 39
Helical Capsids 41
Icosahedral (Isometric) Capsids 46
Enveloped Viruses 52
Complex Virus Structures 56
Protein–Nucleic Acid Interactions and Genome Packaging 61
Virus Receptors: Recognition and Binding 66
Other Interactions of the Virus Capsid with the Host Cell 66
Summary 67
Further Reading 67
3 Genomes 70
The Structure and Complexity of Virus Genomes 70
Molecular Genetics 73
Virus Genetics 76
Virus Mutants 77
Genetic Interactions between Viruses 80
Nongenetic Interactions between Viruses 83
Small DNA Genomes 85
Large DNA Genomes 89
Positive-Strand RNA Viruses 92
Picornaviruses 93
Togaviruses 94
Flaviviruses 94
Coronaviruses 94
Positive-Sense RNA Plant Viruses 95
Negative-Strand RNA Viruses 96
Bunyaviruses 97
Arenaviruses 97
Orthomyxoviruses 98
Paramyxoviruses 98
Rhabdoviruses 98
Segmented and Multipartite Virus Genomes 98
Reverse Transcription and Transposition 102
The Virome—Evolution and Epidemiology 111
Summary 114
Further Reading 114
4 Replication 116
Overview of Virus Replication 116
Investigation of Virus Replication 117
The Replication Cycle 123
Attachment 123
Penetration 129
Uncoating 131
Genome Replication and Gene Expression 133
Assembly 138
Maturation 139
Release 141
Summary 143
Further Reading 144
5 Expression 146
Expression of Genetic Information 146
Control of Prokaryote Gene Expression 147
Control of Expression in Bacteriophage . 148
Control of Eukaryote Gene Expression 153
Genome Coding Strategies 156
Class I: Double-Stranded DNA 156
Polyomaviruses and Papillomaviruses 157
Adenoviruses 157
Herpesviruses 157
Poxviruses 158
The Giant Viruses: Mimivirus, Megavirus, Pandoravirus, Pithovirus 159
Class II: Single-Stranded DNA 159
Class III: Double-Stranded RNA 160
Class IV: Single-Stranded (+)Sense RNA 162
Class V: Single-Stranded (-)Sense RNA 165
Class VI: Single-Stranded (+)Sense RNA with DNA Intermediate 167
Class VII: Double-Stranded DNA with RNA Intermediate 167
Transcriptional Control of Expression 168
Posttranscriptional Control of Expression 172
Summary 181
Further Reading 181
6 Infection 184
Virus Infections of Plants 184
Immune Responses to Virus Infections in Animals 189
Viruses and Apoptosis 194
Interferons 196
Evasion of Immune Responses by Viruses 201
Inhibition of MHC-I-Restricted Antigen Presentation 202
Inhibition of MHC-II-Restricted Antigen Presentation 202
Inhibition of NK Cell Lysis 202
Interference with Apoptosis 202
Inhibition of Cytokine Action 202
Evasion of Humoral Immunity 203
Evasion of the Complement Cascade 203
Virus–Host Interactions 203
The Course of Virus Infections 213
Abortive Infection 213
Acute Infection 213
Chronic Infection 213
Persistent Infection 213
Latent Infection 215
Prevention and Therapy of Virus Infection 216
RNA Interference 220
Viruses as Therapeutics 223
Chemotherapy of Virus Infections 225
Summary 230
Further Reading 230
7 Pathogenesis 232
Mechanisms of Cellular Injury 233
Viruses and Immunodeficiency 236
Virus-Related Diseases 241
Bacteriophages and Human Disease 244
Cell Transformation by Viruses 245
Cell Transformation by Retroviruses 250
Cell Transformation by DNA Viruses 252
Viruses and Cancer 255
New and Emergent Viruses 260
Zoonoses 267
Bioterrorism 268
Summary 269
Further Reading 269
8 Subviral Agents: Genomes without Viruses, Viruses without Genomes 272
Satellites and Viroids 272
Prions 276
Pathology of Prion Diseases 277
TSE in Animals 277
Scrapie 277
Transmissible Mink Encephalopathy (TME) 279
Feline Spongiform Encephalopathy (FSE) 279
Chronic Wasting Disease (CWD) 279
Bovine Spongiform Encephalopathy 280
Human TSEs 281
Molecular Biology of Prions 284
Summary 290
Further Reading 290
Appendix 1: Glossary and Abbreviations 292
Appendix 2: Classification of Subcellular Infectious Agents 302
Appendix 3: The History of Virology 306
Index 312

Textauszug

Chapter 2

Particles

This chapter considers why viruses make particles to contain their genomes. In order to understand how virus particles are put together, it explains how symmetry allows particles to assemble using only the information contained within the particle. It finishes by looking at the main types of virus particle—helical and icosahedral—as well as more complex structures and considers how the virus coat interacts with the host cell.

Keywords

Capsids; coat proteins; genome packaging; particles; symmetry; virions

Contents

The Function and Formation of Virus Particles 27

Capsid Symmetry and Virus Architecture 28

Helical Capsids 30

Icosahedral (Isometric) Capsids 35

Enveloped Viruses 41

Complex Virus Structures 45

Protein–Nucleic Acid Interactions and Genome Packaging 50

Virus Receptors: Recognition and Binding 55

Other Interactions of the Virus Capsid with the Host Cell 55

Summary 56

Intended Learning Outcomes

On completing this chapter you should be able to:

 Explain the need for viruses to form outer coats.

 Discuss the role of symmetry in the formation of virus particles.

 Describe examples of different types of virus particles, from simple to more complex forms.

The Function and Formation of Virus Particles

Figure 2.1 shows an illustration of the approximate shapes and sizes of different families of viruses. Virus particles may range in size by nearly 100-fold, from around 17 nm (Porcine circovirus) to 1,200 nm in length (Pithovirus sibericum). The protein subunits in a virus capsid are redundant, that is, there are many copies in each particle. Damage to one or more capsid subunits may make that particular subunit nonfunctional, but rarely does limited damage destroy the infectivity of the entire particle. This helps make the capsid an effective barrier. The protein shells surrounding virus particles are very tough, about as strong as a hard plastic such as Perspex or Plexiglas, although they are only a billionth of a meter or so in diameter. They are also elastic and are able to deform by up to a third without breaking. This combination of strength, flexibility, and small size means that it is physically difficult (although not impossible) to break open virus particles by physical pressure.

Box 2.1

Why Bother?

Why do viruses bother to form a particle to contain their genome? Some unusual and infectious agents such as viroids (see Chapter 8) don’t. The fact that viruses pay the genetic and biochemical cost of encoding and assembling the components of a particle shows there must be some benefits. At the simplest level, the function of the outer shells of a virus particle is to protect the fragile nucleic acid genome from physical, chemical, or enzyme damage. After leaving the host cell, the virus enters a hostile environment that would quickly inactivate an unprotected genome. Nucleic acids are susceptible to physical damage such as shearing by mechanical forces, and to chemical modification by ultraviolet light (sunlight). The natural environment is full of nucleases from dead cells or deliberately secreted as defense against infection. In viruses with single-stranded genomes, breaking a single phosphodiester bond in the backbone of the genome or chemical modification of one nucleotide is sufficient to inactivate that virus particle, making replication of the genome impossible. Particles offer protection, but they also allow the virus to communicate with a host cell.

Figure 2.1 Shapes and sizes of virus particles.
A diagram illustrating the shapes and sizes of viruses of families. The virions are drawn approximately to scale, but artistic license has been used in representing their structure. In some, the cross-sectional structures of capsid and envelope are shown, with a representation of the genome. For the very small virions, only their size and symmetry are depicted. From F.A. Murphy, School of Veterinary Medicine, University of California, Davis. http://www.vetmed.ucdavis.edu/viruses/VirusDiagram.html

The outer surface of the virus is also responsible for recognition of and interaction with the host cell. Initially, this takes the form of binding of a specific virus-attachment protein to a cellular receptor molecule. However, the capsid also has a role to play in initiating infection by delivering the genome in a form in which it can interact with the host cell. In some cases, this is a simple process that consists only of dumping the genome into the cytoplasm of the cell. In other cases, this process is much more complex, for example, retroviruses carry out extensive modifications to the virus genome while it is still inside the particle, converting two molecules of single-stranded RNA to one molecule of double-stranded DNA before delivering it to the cell nucleus. Beyond protecting the genome, this function of the capsid is vital in allowing viruses to establish an infection.

In order to form particles, viruses must overcome two fundamental problems. First, they must assemble the particle using only the information available from the components that make up the particle itself. Second, virus particles form regular geometric shapes, even though the proteins from which they are made are irregular. How do these simple organisms solve these difficulties? The solutions to both problems lie in the rules of symmetry.

Capsid Symmetry and Virus Architecture

It is possible to imagine a virus particle, the outer shell of which (the capsid) consists of a single, hollow protein molecule, which folds up trapping the virus genome inside. In practice, this arrangement cannot occur, for the following reason. The triplet nature of the genetic code means that three nucleotides (or base pairs, in the case of viruses with double-stranded genomes) are necessary to encode one amino acid. As parasites, viruses cannot use an alternative, more economical, genetic code because this could not be read by the host cell. Because the approximate molecular weight of a nucleotide triplet is 1,000 g/mol and the average molecular weight of a single amino acid is 150 g/mol, a nucleic acid can only encode a protein that is at most 15% of its own weight. For this reason, virus capsids must be made up of multiple protein molecules (subunit construction), and viruses must solve the problem of how these subunits are arranged to form a stable structure.

In 1957, Fraenkel-Conrat and Williams showed that when mixtures of purified tobacco mosaic virus (TMV) RNA and coat protein are incubated together, virus particles formed. The discovery that virus particles could form spontaneously from purified subunits without any extra information indicates that the particle is in the free energy minimum state and is the most energetically favored structure of the components. This inherent stability is an important feature of virus particles. Although some viruses are very fragile and unable to survive outside the protected host cell environment, many are able to persist for long periods, in some cases for years.

The forces that drive the assembly of virus particles include hydrophobic and electrostatic interactions. Only rarely are covalent bonds involved in holding together the subunits. In biological terms, this means that protein–protein, protein–nucleic acid, and protein–lipid interactions are involved. We now have a good understanding of general principles and repeated structural motifs that appear to govern the construction of many diverse, unrelated viruses. These are discussed below under the two main classes of virus structures: helical and icosahedral symmetry.

Helical Capsids

TMV is representative of one of the two major structural classes seen in virus particles, those with helical symmetry. The simplest way to arrange multiple, identical protein subunits is to use rotational symmetry and to arrange the irregularly shaped proteins around the circumference of a circle to form a disk. Multiple disks can then be stacked on top of one another to form a cylinder, with the virus genome coated by the protein shell or contained in the hollow center of the cylinder. Denaturation studies of TMV suggest that this is the form this virus particle takes (see Chapter 1).

Closer examination of the TMV particle by X-ray crystallography reveals that the structure of the capsid actually consists of a helix rather than a pile of stacked disks. A helix can be defined mathematically by two parameters: its amplitude (diameter) and pitch (the distance covered by each complete turn of the helix) (Figure 2.2). Helices are simple structures formed by stacking repeated components with a constant association (amplitude and pitch) to one another. If this simple relationship is broken, a spiral forms rather than a helix, and a spiral is unsuitable for containing and protecting a virus genome. In terms of individual protein subunits, helices are described by the number of...

Produkt-Details

• Erscheint lt. Verlag: 6.3.2015
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• Themenwelt: Studium ► Querschnittsbereiche ► Infektiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie ► Mikrobiologie / Immunologie
• Themenwelt: Technik
• ISBN-10: 0-12-801955-7 / 0128019557
• ISBN-13: 978-0-12-801955-9 / 9780128019559