Principles of Virology

, by Flint, S. Jane; Enquist, L. W.; Krug, R. M.; Racaniello, V. R.; Skalka, A. M.; Flint, S. Jane

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ISBN: 9781555811273 | 1555811272
Cover: Hardcover
Copyright: 11/1/1999

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Designed to fill the existing gap between simple introductory texts and very advanced reviews of major virus families, Principles of Virology introduces upper-level undergraduates, graduate students, and medical students to all aspects of virology. Written in an engagingly readable style and generously illustrated with over 400 full-color illustrations, this approachable volume offers detailed examples that illustrate common principles, specific strategies adopted by different viruses to ensure their reproduction, and the current state of virology research.

Acknowledgments

xix

Organization of This Book

xxiii

I The Science of Virology

(56)

Foundations of Virology

(22)

Luria's Credo

(1)

Virus Prehistory

(5)

Viral Infections in Antiquity

(1)

The First Vaccines

(2)

Microorganisms as Pathogenic Agents

(2)

The Discovery of Viruses

(3)

The First Viruses

(2)

Identification of Human Viruses

(1)

The Definitive Properties of Viruses

(4)

The Structural Simplicity of Viruses

(1)

The Intracellular Parasitism of Viruses

(4)

Viruses Defined

(1)

Cataloging of Diverse Animal Viruses

(4)

Many Sizes and Shapes Produced by Evolution

(3)

Genetic Content

(1)

Capsid Symmetry

(1)

Enveloped or Naked Particles

(1)

Virion Enzymes

(1)

Unifying Principles

(1)

A Common Strategy

(1)

Highlights of Virus Strategies Outlined in This Book

(1)

References

(3)

Virus Cultivation, Detection, and Genetics

(33)

Introduction

(1)

Cultivation of Viruses

(4)

Cell Culture

(2)

Embryonated Eggs

(1)

Laboratory Animals

(1)

Detection of Viruses in the Host

(13)

Measurement of Infectious Units

(4)

Measurement of Virus Particles and Their Components

(7)

The One-Step Growth Cycle

(2)

Genetic Analysis of Viruses

(13)

Classical Genetic Methods

(2)

Engineering Mutations into Viruses

(7)

Engineering Viral Genomes: Viral Vectors

(4)

Perspectives

(1)

References

(2)

II Molecular Biology

(420)

Virus Structure

(42)

Introduction

(6)

Functions of the Virion

(1)

Nomenclature

(2)

Methods for Studying Virus Structure

(3)

Building a Protective Coat

(22)

Helical Structures

(1)

Capsids or Nucleocapsids with Icosahedral Symmetry

(18)

Complex Viruses

(3)

Packaging the Nucleic Acid Genome

(2)

Direct Contact of the Genome with Proteins of the Outer Shell

(1)

Packaging by Specialized Virion Proteins

(1)

Packaging by Cellular Proteins

(1)

Viruses with Envelopes

(5)

Viral Envelope Components

(2)

Simple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or Nucleocapsid

(1)

Enveloped Viruses with Additional Protein Layers

(2)

Other Components of Virions

(2)

Virion Enzymes

(1)

Other Viral Proteins

(1)

Cellular Macromolecules

(1)

Perspectives

(1)

References

(3)

Virus Attachment to Host Cells

100

(32)

Introduction

101

(1)

Protection and Release of Genetic Material

102

(1)

Finding the Right Cells To Infect

102

(1)

The Architecture of Cell Surfaces

102

(4)

Extracellular Matrix: Components and Biological Importance

103

(1)

Properties of the Plasma Membrane

103

(2)

Cell Membrane Proteins

105

(1)

Interaction of Viruses with Cell Receptors

106

(22)

General Principles

106

(6)

Identification of Viral Receptors on Cells

112

(11)

How Virions Attach to Receptors

123

(5)

Perspectives

128

(1)

References

129

(3)

Virus Entry into Cells

132

(30)

Introduction

133

(1)

Uptake of Macromolecules by Cells

134

(3)

The Plasma Membrane Is a Semipermeable Barrier

134

(1)

Cells Take Up Macromolecules by Phagocytosis and Endocytosis

134

(2)

Cell Membranes Fuse during Endocytosis

136

(1)

Mechanisms of Virus Entry into Cells

137

(15)

Uncoating at the Plasma Membrane

137

(5)

Virus Entry via the Endocytic Pathway

142

(5)

Entry of Nonenveloped Viruses into Cells

147

(4)

Cellular Molecules That Play Roles in Virus Uncoating

151

(1)

Transport of the Viral Genome into the Nucleus

152

(7)

The Cellular Pathway of Protein Import into the Nucleus

152

(4)

Import of DNA Genomes

156

(1)

Import of the Retroviral Genome into the Nucleus

157

(2)

Import of Influenza Virus RNP into the Cell Nucleus

159

(1)

Perspectives

159

(1)

References

160

(2)

Genome Replication and mRNA Production by RNA Viruses

162

(36)

Introduction

163

(1)

Mechanisms of Viral RNA Synthesis

164

(21)

RNA-Dependent RNA Polymerases

164

(4)

Accessory Proteins in RNA-Dependent RNA Synthesis

168

(4)

The Nature of the RNA Template

172

(2)

Initiation and Elongation

174

(9)

Cellular Sites of Viral RNA Synthesis

183

(1)

Unique Mechanisms of mRNA and Genome Synthesis of the Hepatitis Delta Satellite Virus

184

(1)

The Switch from mRNA Production to Genome RNA Synthesis

185

(5)

Regulation of Initiation: Different Polymerase Specificities

187

(1)

Suppression of Intergenic Stop-Start Reactions by Nucleocapsid Protein

188

(1)

Antitermination and Different RNA Polymerases

189

(1)

Suppression of Termination Caused by a Stem-Loop Structure

189

(1)

Different Templates Used for mRNA Synthesis and Genome Replication

189

(1)

Suppression of Polyadenylation

190

(1)

Origins of Diversity in RNA Viruses

190

(4)

Misincorporation of Nucleotides

190

(1)

Segment Reassortment and RNA Recombination

191

(1)

RNA Recombination Leading to the Production of Pathogenic Viruses

192

(1)

RNA Recombination Leading to the Production of Defective-Interfering RNAs

192

(1)

RNA Editing

193

(1)

Perspectives

194

(1)

References

194

(4)

Reverse Transcription and Integration: Hallmarks of the Retroid Viruses

198

(38)

Retroviral Reverse Transcription

199

(15)

Introduction

199

(1)

The Pathway of Retroviral Reverse Transcription

200

(7)

General Properties and Structure of Retroviral Reverse Transcriptases

207

(5)

Other Examples of Reverse Transcription

212

(2)

Retroviral DNA Integration

214

(10)

Introduction

214

(1)

Pathway of Retroviral Integration

214

(5)

Integrase Structure and Mechanism

219

(5)

Hepadnaviral Reverse Transcription

224

(8)

Introduction

224

(1)

Pathway of Reverse Transcription

225

(7)

Perspectives

232

(1)

Comparison of Systems

232

(1)

References

233

(3)

Transcription Strategies: DNA Templates

236

(50)

Introduction

237

(1)

Properties of Cellular and Viral Transcription Systems

238

(14)

Cellular Transcription Systems Used by Viruses

238

(1)

Production of Viral DNA Templates Transcribed by Cellular RNA Polymerases

238

(2)

Transcription by RNA Polymerase II

240

(12)

Transcription of Viral DNA Templates by the Cellular Machinery Alone

252

(1)

Viral Proteins That Regulate Transcription by RNA Polymerase II

253

(24)

Patterns of Regulation by Viral Proteins

253

(1)

Autoregulation by the Human Immunodeficiency Virus Type 1 Tat Protein

253

(8)

The Transcriptional Cascades of DNA Viruses

261

(16)

A Viral DNA-Dependent RNA Polymerase

277

(1)

Transcription of Viral Genes by RNA Polymerase III

278

(2)

Transcription of the Adenoviral VA-RNA Genes

279

(1)

Virus-Specific Applications of Cellular Transcription Components

280

(1)

Inhibition of the Cellular Transcription Machinery in Virus-Infected Cells

281

(1)

Perspectives

281

(1)

References

282

(4)

Genome Replication Strategies: DNA Viruses

286

(44)

Introduction

287

(2)

DNA Synthesis by the Cellular Replication Machinery: Lessons from Simian Virus 40

289

(10)

Eukaryotic Replicons

289

(3)

Cellular Replication Proteins and Their Functions during Simian Virus 40 DNA Synthesis

292

(7)

Mechanisms of Viral DNA Synthesis

299

(16)

Priming and Elongation

299

(4)

Viral Replication Origins and Their Recognition

303

(8)

Viral DNA Synthesis Machinery

311

(2)

Resolution and Processing of Viral Replication Products

313

(2)

Mechanisms of Exponential Viral DNA Replication

315

(5)

Induction of Synthesis of Cellular Replication Proteins by Viral Gene Products

315

(3)

Synthesis of Large Sets of Viral Replication Proteins

318

(1)

Viral DNA Replication Independent of Cellular Proteins

318

(1)

Delayed Synthesis of Virion Structural Proteins

318

(1)

Inhibition of Cellular DNA Synthesis

319

(1)

Localization of Replicating Viral DNA to Specialized Intracellular Sites

319

(1)

Limited Replication of Viral DNA

320

(3)

Replication as Part of the Cellular Genome: Integrated Parvoviral DNA

320

(1)

Regulation of Replication via Different Viral Origins: Epstein-Barr Virus

321

(1)

Controlled and Exponential Replication from a Single Origin: the Papillomaviruses

322

(1)

Origins of Genetic Diversity in DNA Viruses

323

(3)

Fidelity of Replication by Viral DNA Polymerases

323

(1)

Recombination of Viral Genomes

324

(2)

Perspectives

326

(1)

References

327

(3)

Processing of Viral Pre-mRNA

330

(40)

Introduction

331

(2)

Covalent Modification during Viral Pre-mRNA Processing

333

(18)

Capping the 5' Ends of Viral mRNA

333

(4)

Synthesis of 3' Poly (A) Segments of Viral mRNA

337

(2)

Splicing of Viral Pre-mRNA

339

(6)

Alternative Splicing of Viral Pre-mRNA

345

(3)

Interactions Between Polyadenylation and Splicing in Viral Gene Expression

348

(3)

Editing of Viral mRNAs

351

(1)

Export of Viral and Cellular RNAs from the Nucleus

351

(7)

The Cellular Export Machinery

352

(1)

Export of Viral mRNA

353

(5)

Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins

358

(5)

Temporal Control of Viral Gene Expression

358

(3)

Inhibition of Cellular mRNA Production by Viral Proteins

361

(2)

Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm

363

(2)

Regulation of mRNA Stability by a Viral Protein

363

(1)

Regulation of mRNA Stability in Transformation

364

(1)

Perspectives

365

(1)

References

366

(4)

Translational Control of Viral Gene Expression

370

(32)

Introduction

371

(1)

Mechanisms of Eukaryotic Protein Synthesis

372

(12)

General Structure of Eukaryotic mRNA

372

(1)

The Translational Machinery

372

(1)

Initiation

373

(10)

Elongation and Termination

383

(1)

The Diversity of Viral Translation Strategies

384

(7)

Polyprotein Synthesis

384

(2)

Leaky Scanning

386

(2)

Reinitiation

388

(1)

Suppression of Termination

388

(2)

Ribosomal Frameshifting

390

(1)

Regulation of Translation during Viral Infection

391

(7)

Inhibition of Translation as a Cellular Defense against Viral Infection

392

(3)

Regulation of eIF4F Activity

395

(3)

Perspectives

398

(1)

References

399

(3)

Intracellular Transport of Viral Components: Prelude to Assembly

402

(36)

Introduction

403

(1)

Assembly within the Nucleus

404

(2)

Import of Viral Proteins for Assembly

404

(2)

Assembly at the Plasma Membrane

406

(23)

The Cellular Pathway by Which Viral Membrane Proteins Are Transported to the Plasma Membrane

406

(12)

Viral Proteins in the Secretory Pathway

418

(3)

Sorting of Viral Proteins in Polarized Cells

421

(3)

Inhibition of Transport of Cellular Proteins by Viral Infection

424

(1)

Signal Sequence-Independent Transport of Viral Proteins to the Plasma Membrane

425

(4)

Interactions with Internal Cellular Membranes

429

(2)

Localization of Viral Proteins to Compartments of the Secretory Pathway

429

(1)

Localization of Viral Proteins to the Nuclear Membrane

430

(1)

Transport of Viral Genomes to Assembly Sites

431

(2)

Genome RNA Transport from the Nucleus to the Cytoplasm

432

(1)

RNA Transport from the Cytoplasm to the Plasma Membrane

432

(1)

Perspectives

433

(1)

References

434

(4)

Assembly, Exit, and Maturation of Progeny Virions

438

(39)

Introduction

439

(1)

Methods of Studying Virus Assembly and Egress

440

(3)

Structural Studies of Virus Particles

440

(1)

Visualization of Assembly and Exit by Electron Microscopy

441

(1)

Biochemical and Genetic Analysis of Assembly Intermediates

441

(2)

Methods Based on Recombinant DNA Technology

443

(1)

Assembly of Protein Shells

443

(9)

Formation of Structural Units

443

(3)

Capsid and Nucleocapsid Assembly

446

(2)

Self-Assembly and Assisted Assembly Reactions

448

(4)

Selective Packaging of the Viral Genome and Other Virion Components

452

(8)

Concerted or Sequential Assembly

452

(1)

Recognition and Packaging of the Nucleic Acid Genome

452

(8)

Incorporation of Virion Enzymes and Other Nonstructural Proteins

460

(1)

Acquisition of an Envelope

460

(3)

Sequential Assembly of Internal Components and Budding from a Cellular Membrane

460

(1)

Coordination of the Assembly of Internal Structures with the Acquisition of the Envelope

461

(2)

Release of Virus Particles

463

(4)

Release of Nonenveloped Viruses

463

(1)

Assembly at Internal Membranes: the Problem of Exocytosis

464

(3)

Maturation of Progeny Virions

467

(5)

Proteolytic Processing of Virion Proteins

467

(3)

Other Maturation Reactions

470

(2)

Cell-to-Cell Spread

472

(1)

Perspectives

473

(1)

References

473

(4)

III Pathogenesis and Control

477

(272)

Virus Offense Meets Host Defense

478

(40)

The Host Defense Against Viral Infections

479

(5)

Primary Defenses

479

(1)

Immune Defenses

480

(4)

The Innate Immune Response

484

(9)

Cytokines

484

(1)

Interferons

485

(4)

Complement

489

(3)

Collectins

492

(1)

NK Cells

492

(1)

The Adaptive Immune Response

493

(18)

General Features

493

(3)

Cells of the Adaptive Immune System

496

(6)

Antigen Presentation and Activation of Immune Cells

502

(4)

The Cell-Mediated Adaptive Response

506

(2)

The Antibody Response

508

(3)

Perspectives

511

(4)

References

515

(3)

Patterns of Infection: a Delicate Balance

518

(34)

Introduction

519

(1)

Infection Strategies

519

(1)

Life Cycles and Patterns of Viral Infections

519

(1)

Initiating an Infection

520

(11)

Basic Requirements

520

(1)

Tropism

521

(1)

Successful Infections Must Evade Host Defenses

521

(10)

Many Other Variables Govern the Result of Infection

531

(1)

Acute Infections

531

(4)

Definition and Requirements

531

(2)

Acute Infections Present Common Public Health Problems

533

(1)

Defense against Acute Infections

534

(1)

Multiple Acute Infections in a Single Host

534

(1)

Pathogenic Effects of an Acute Infection

535

(1)

Persistent Infections

535

(5)

Definition and Requirements

535

(1)

Infection of Tissues with Reduced Immune Surveillance

536

(1)

Direct Infection of the Immune System Itself

537

(1)

Two Viruses That Cause Persistent Infections

538

(2)

Latent Infections

540

(6)

An Extreme Variation of the Persistent Infection

540

(1)

Two Viruses That Produce Latent Infections

540

(6)

Slow Infections

546

(3)

Sigurdsson's Legacy: Icelandic Sheep and Fatal Degenerative Diseases

546

(1)

Slow Viruses and "Unconventional Agents"

546

(3)

Other Patterns of Viral Infections

549

(1)

Abortive Infections

549

(1)

Transforming Infections

550

(1)

Perspectives

550

(1)

References

550

(2)

Viral Transformation and Oncogenesis

552

(42)

Introduction

553

(9)

Properties of Transformed Cells

554

(3)

Control of Cell Growth and Division

557

(5)

Oncogenic Viruses

562

(9)

Discovery of Oncogenic Viruses

562

(2)

Viral Genetic Information in Transformed Cells

564

(5)

The Origin and Nature of Viral Transforming Genes

569

(2)

Functions of Viral Transforming Proteins

571

(1)

Viral Transformation by Activation of Cellular Signal Transduction Pathways

571

(11)

Viral Mimics of Cellular Signaling Molecules

572

(4)

Virus-Specific Signal Transduction Molecules

576

(1)

Alteration of the Expression or Activity of Cellular Signal Transduction Proteins

576

(6)

Viral Transformation via Cell Cycle Control Pathways

582

(7)

Abrogation of Restriction Point Control Exerted by the Rb Protein

582

(1)

Inhibition of Negative Regulation by Rb-Related Proteins

583

(3)

Production of Virus-Specific Cyclins

586

(1)

Inhibition of p53 Functions

586

(3)

Other Mechanisms of Viral Transformation and Oncogenesis

589

(2)

Nontransducing Complex Oncogenic Retroviruses: Tumorigenesis with Very Long Latency

589

(1)

Hepadnaviral Oncogenesis

590

(1)

"Hit-and-Run" Transformation by Herpes Simplex Viruses?

590

(1)

Perspectives

591

(1)

References

592

(2)

Viral Pathogenesis

594

(36)

Introduction

595

(1)

Viral Dissemination in the Host

595

(19)

Viral Entry

595

(5)

Viral Spread

600

(6)

Tissue Invasion

606

(3)

Tropism

609

(3)

Virus Shedding and Transmission

612

(2)

Viral Virulence

614

(5)

Measuring Viral Virulence

615

(1)

Genetic Determinants of Virulence

615

(4)

Injury Induced by Viruses

619

(6)

Direct Effects of Primary Infection by Cytolytic Viruses

619

(1)

Pathogenic Effects of Noncytolytic Viruses

620

(1)

Immunopathology: Indirect Effects of Viral Infection

620

(5)

Host Susceptibility to Viral Disease

625

(1)

Genetic Determinants of Susceptibility

625

(1)

Nongenetic Determinants of Susceptibility

626

(1)

Perspectives

626

(1)

References

627

(3)

Multiple Facets of Human Immunodeficiency Virus Pathogenicity

630

(32)

Introduction

631

(1)

Worldwide Scope of the Problem

631

(1)

HIV Is a Lentivirus

632

(6)

Discovery and Characterization

632

(2)

Distinctive Features of the HIV Replication Cycle and the Roles of Auxiliary Proteins

634

(4)

Cellular Targets

638

(2)

Routes of Transmission

640

(2)

Sources of Virus Infection

640

(1)

Modes of Transmission

640

(1)

Mechanics of Spread

641

(1)

The Course of Infection

642

(2)

Patterns of Virus Appearance and Immune Cell Indicators of Infection

642

(1)

Variability of Response to Infection

643

(1)

Origins of Cellular Immune Dysfunction

644

(2)

CD4+ T Lymphocytes

644

(1)

CD8+ T Lymphocytes

644

(1)

Monocytes and Macrophages

644

(1)

B Cells

645

(1)

Natural Killer Cells

645

(1)

Autoimmunity

645

(1)

Immune Response to HIV

646

(3)

Humoral Responses

646

(2)

The Cellular Immune Response

648

(1)

Summary: the Critical Balance

648

(1)

Dynamics of HIV-1 Replication in AIDS Patients

649

(1)

Effects of HIV on Different Tissues and Organ Systems

650

(4)

Lymphoid Organs

650

(2)

The Nervous System

652

(2)

The Gastrointestinal System

654

(1)

Other Organ Systems

654

(1)

HIV and Cancer

654

(3)

Kaposi's Sarcoma

654

(1)

B-Cell Lymphomas

655

(1)

Anogenital Carcinomas

656

(1)

Prospects for Treatment and Prevention

657

(3)

Antiviral Drugs and Therapies

657

(2)

Vaccine Development

659

(1)

Perspectives

660

(1)

References

661

(1)

Prevention and Control of Viral Diseases

662

(54)

Introduction

663

(1)

Vaccines: the Proven Best Defense against Viruses

664

(2)

Smallpox: a Historical Perspective

664

(1)

Large-Scale Vaccination Programs Can Be Dramatically Effective

664

(2)

Preparation of Vaccines

666

(12)

The Fundamental Challenge

666

(1)

Vaccine Basics

666

(4)

Three Types of Vaccines

670

(8)

New Vaccine Technology

678

(5)

Viral Vectors

678

(1)

DNA Vaccines

678

(4)

Vaccine Delivery Technology

682

(1)

Immunotherapy

682

(1)

Antiviral Drugs: Small Molecules That Block Virus Replication

683

(19)

Paradox: So Much Knowledge, So Few Antivirals

683

(1)

Historical Perspective

683

(1)

Discovering Antiviral Compounds

684

(1)

Screening for Antiviral Compounds

685

(2)

Designer Antivirals and Computer-Based Searching

687

(3)

The Difference between "R" and "D"

690

(1)

Examples of Commercially Available Antiviral Drugs for Viruses other than HIV

691

(5)

New Targets for Antiviral Drugs

696

(3)

Antiviral Gene Therapy and Transdominant Inhibitors

699

(2)

Resistance to Antiviral Drugs

701

(1)

HIV and AIDS

702

(10)

Examples of Drugs Approved by the Food and Drug Administration for Treatment of HIV Infection

702

(5)

The Problem of Drug Resistance and the Use of Combination Therapy To Combat HIV Infection

707

(2)

Combination Therapy

709

(2)

The Quest for an AIDS Vaccine

711

(1)

Perspectives

712

(1)

References

712

(4)

Virus Evolution and the Emergence of New Viruses

716

(33)

Virus Evolution

717

(12)

Virus Evolution Is Contemporary

717

(1)

How Do Viruses Evolve?

717

(5)

The Origin of Viruses

722

(5)

Evolution Is Constrained by the Fundamental Properties of Viruses

727

(2)

Emerging Viruses

729

(13)

The Spectrum of Host-Virus Interactions

729

(6)

Known Viruses Can Expand Their Niche because of Changing Host Populations and Environment

735

(4)

Known Viruses Can Expand Their Host Range or Pathogenicity by Mutation or Recombination

739

(2)

Some Emergent Viruses Are Truly Novel

741

(1)

A Paradigm Shift in Diagnostic Virology

742

(1)

Perceptions and Possibilities

742

(4)

Infectious Agents and Public Perceptions

742

(1)

What Next?

743

(3)

Perspectives

746

(1)

References

746

(3)

Appendix: Structure, Genome Organization, and Infectious Cycles of Selected Animal Viruses Discussed in This Book

749

(32)

Index

781

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Principles of Virology

Summary

Table of Contents

Supplemental Materials