Principles of Virology, the leading virology textbook in use, is an extremely valuable and highly informative presentation of virology at the interface of modern cell biology and immunology. This text utilizes a uniquely rational approach by highlighting common principles and processes across all viruses. Using a set of representative viruses to illustrate the breadth of viral complexity, students are able to under-stand viral reproduction and pathogenesis and are equipped with the necessary tools for future encounters with new or understudied viruses.

This fifth edition was updated to keep pace with the ever-changing field of virology. In addition to the beloved full-color illustrations, video interviews with leading scientists, movies, and links to exciting blogposts on relevant topics, this edition includes study questions and active learning puzzles in each chapter, as well as short descriptions regarding the key messages of references of special interest. 

Volume I: Molecular Biology focuses on the molecular processes of viral reproduction, from entry through release. Volume II: Pathogenesis and Control addresses the interplay between viruses and their host organisms, on both the micro- and macroscale, including chapters on public health, the immune response, vaccines and other antiviral strategies, viral evolution, and a brand new chapter on the therapeutic uses of viruses. These two volumes can be used for separate courses or together in a single course. Each includes a unique appendix, glossary, and links to internet resources.

Principles of Virology, Fifth Edition, is ideal for teaching the strategies by which all viruses reproduce, spread within a host, and are maintained within populations. This edition carefully reflects the results of extensive vetting and feedback received from course instructors and students, making this renowned textbook even more appropriate for undergraduate and graduate courses in virology, microbiology, and infectious diseases.

Volume 1

Preface

Acknowledgments

About the Authors

PART I: The Science of Virology

1 Foundations

Luria&s Credo

Viruses Defined

Why We Study Viruses

Viruses Are Everywhere

Viruses Infect All Living Things

Viruses Can Cause Human Disease

Viruses Can Be Beneficial

Viruses \"R\" Us

Viruses Can Cross Species Boundaries

Viruses Are Unique Tools To Study Biology

Virus Prehistory

Viral Infections in Antiquity

The First Vaccines Microorganisms as Pathogenic Agents

Discovery of Viruses

The Defining Properties of Viruses

The Structural Simplicity of Virus Particles

The Intracellular Parasitism of Viruses

Cataloging Animal Viruses

The Classical System

Classification by Genome Type: the  Baltimore System

A Common Strategy for Viral Propagation

Perspectives

References

Study Questions

2 The Infectious Cycle

Introduction

The Infectious Cycle

The Cell

Entering Cells

Viral RNA Synthesis

Viral Protein Synthesis

Viral Genome Replication

Assembly of Progeny Virus Particles

Viral Pathogenesis

Overcoming Host Defenses

Cultivation of Viruses

Cell Culture

Embryonated Eggs

Laboratory Animals

Assay of Viruses

Measurement of Infectious Units

Efficiency of Plating

Measurement of Virus Particles

Viral Reproduction: the Burst Concept

The One-Step Growth Cycle

One-Step Growth Analysis: a Valuable Tool for Studying Animal Viruses

Global Analysis

DNA Microarrays

Mass Spectrometry

Protein-Protein Interactions

Single-Cell Virology

Perspectives

References

Study Questions

PART II: Molecular Biology

3 Genomes and Genetics

Introduction

Genome Principles and the Baltimore System

Structure and Complexity of Viral Genomes

DNA Genomes

RNA Genomes

What Do Viral Genomes Look Like?

Coding Strategies

What Can Viral Sequences Tell Us?

The \"Big and Small\" of Viral Genomes: Does Size Matter?

The Origin of Viral Genomes

Genetic Analysis of Viruses

Classical Genetic Methods

Engineering Mutations into Viral Genomes

Engineering Viral Genomes: Viral Vectors

Perspectives

References

Study Questions

4 Structure

Introduction

Functions of the Virion

Nomenclature

Methods for Studying Virus Structure

Building a Protective Coat

Helical Structures

Capsids with Icosahedral Symmetry

Other Capsid Architectures

Packaging the Nucleic Acid Genome

Direct Contact of the Genome with a Protein Shell

Packaging by Specialized Viral Proteins

Packaging by Cellular Proteins

Viruses with Envelopes

Viral Envelope Components

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

Enveloped Viruses with an Additional Protein Layer

Large Viruses with Multiple

Structural Elements Particles with Helical or Icosahedral Parts Alternative Architectures

Other Components of Virions

Enzymes

Other Viral Proteins

Cellular Macromolecules

Mechanical Properties of Virus Particles

Investigation of Mechanical Properties of Virus Particles

Stabilization and Destabilization of Virus Particles

Perspectives

References

Study Questions

5 Attachment and Entry

Introduction

Attachment of Virus Particles to Cells

General Principles

Identification of Receptors for Virus Particles

Virus-Receptor Interactions

Entry into Cells

Virus-induced Signaling via Cell Receptors

Routes of entry

Membrane Fusion

Intracellular Trafficking and Uncoating

Movement of Viral and Subviral Particles within Cells

Uncoating of enveloped viruses

Uncoating of non-enveloped viruses

Import of Viral Genomes into the Nucleus

The Nuclear Pore Complex

Nuclear Localization Signals

Import of RNA Genomes

Import of DNA Genomes

Import of Retroviral Genomes

Perspectives

References

Study Questions 

6 Synthesis of RNA from RNA Templates

Introduction

The Nature of the RNA Template

Secondary Structures in Viral RNA

Naked or Nucleocapsid RNA

The RNA Synthesis Machinery

Identification of RNA-Dependent RNA Polymerases

Three-Dimensional Structures of RNA-Dependent RNA Polymerases

Mechanisms of RNA Synthesis

Initiation

Capping

Elongation

Functions of Additional Polymerase Domains

RNA polymerase Oligomerization

Template Specificity

Unwinding the RNA Template

Role of Cellular Proteins

Paradigms for Viral RNA Synthesis

(+) Strand RNA

Synthesis of Nested Subgenomic mRNAs

(−) Strand RNA

Ambisense RNA

Double-Stranded RNA

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

Do Ribosomes and RNA Polymerases Collide?

Origins of Diversity in RNA Virus Genomes

Misincorporation of Nucleotides

Segment Reassortment and RNA Recombination

RNA Editing

Perspectives

References

Study Questions

7 Synthesis of RNA from DNA Templates

Introduction

Properties of Cellular RNA Polymerases That Transcribe Viral DNA

Some Viral Genomes Must Be Converted to Templates Suitable for Transcription

Transcription by RNA Polymerase II

Regulation of RNA Polymerase II Transcription

Common Properties of Proteins That Regulate Transcription

Transcription of Viral DNA Templates by the Cellular Machinery Alone

Viral Proteins That Govern Transcription of DNA Templates

Patterns of Regulation

The Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates Transcription

The Transcriptional Cascades of DNA Viruses

Entry into One of Two Alternative Transcriptional Programs

Transcription of Viral Genes by RNA Polymerase III

The VA-RNA I Promoter

Inhibition of the Cellular Transcriptional Machinery

Unusual Functions of Cellular Transcription Components in Virus-Infected Cells

Viral DNA-Dependent RNA Polymerases

Perspectives

References

Study Questions

8 Processing

Introduction

Covalent Modification during Viral Pre-mRNA Processing

Capping the 5′ Ends of Viral mRNA

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

Internal Methylation of Adenosine Residues

Splicing of Viral Pre-mRNA

Regulated Processing of Viral Pre-mRNA

Editing of Viral mRNAs

Export of RNAs from the Nucleus

The Cellular Export Machinery Export of Viral mRNA

Posttranscriptional Regulation of Viral or Cellular Gene Expression by Viral Proteins

Temporal Control of Viral Gene Expression

Viral Proteins Can Inhibit Cellular mRNA Production

Regulation of Turnover of Viral and Cellular mRNAs in the Cytoplasm

Intrinsic Turnover

Regulation of mRNA Stability by Viral Proteins

mRNA Stabilization Can Facilitate Transformation

Nonsense-Mediated mRNA Decay

Noncoding RNAs

Small Interfering RNAs and Micro-RNAs

Long Noncoding RNAs

Circular RNAs

Perspectives

References

Study Questions

9 Replication of DNA Genomes

Introduction

DNA Synthesis by the Cellular Replication Machinery

Eukaryotic Replicons

Cellular Replication Proteins

Mechanisms of Viral DNA Synthesis

Lessons from Simian Virus 40

Replication of Other Viral DNA Genomes

Properties of Viral Replication Origins

Recognition of Viral Replication Origins

Viral DNA Synthesis Machines

Resolution and Processing of Viral Replication Products

Exponential Accumulation of Viral Genomes

Viral Proteins Can Induce Synthesis of Cellular Replication Proteins

Synthesis of Viral Replication Machines and Accessory Enzymes

Viral DNA Replication Independent of Cellular Proteins

Delayed Synthesis of Structural Proteins Prevents Premature Packaging of DNA Templates

Inhibition of Cellular DNA Synthesis

Synthesis of Viral DNA in Specialized Intracellular Compartments

Limited Replication of Viral DNA Genomes

Integrated Parvoviral DNA Can Be Replicated as Part of the Cellular Genome

Different Viral Origins Regulate Replication of Epstein-Barr Virus

Limited and Amplifying Replication from a Single Origin: the Papillomaviruses

Origins of Genetic Diversity in DNA Viruses

Fidelity of Replication by Viral DNA Polymerases

Modulation of the DNA Damage Response

Recombination of Viral Genomes

Perspectives

References

Study Questions

10 Reverse Transcription and Integration

Retroviral Reverse Transcription

Discovery

Impact

The Process of Reverse Transcription

General Properties and Structure of Retroviral Reverse Transcriptases

Other Examples of Reverse Transcription

Retroviral DNA Integration

The Pathway of Integration: Integrase-Catalyzed Steps

Integrase Structure and Mechanism

Hepadnaviral Reverse Transcription

A DNA Virus with Reverse Transcriptase

The Process of Hepadnaviral Reverse Transcription

Perspectives

References

Study Questions

11 Protein Synthesis

Introduction

Mechanisms of Eukaryotic Protein Synthesis

General Structure of Eukaryotic mRNA

The Translation Machinery

Initiation

Elongation and Termination

The Diversity of Viral Translation Strategies

Polyprotein Synthesis

Leaky Scanning

Reinitiation

StopGo Translation

Suppression of Termination

Ribosomal Frameshifting

Bicistronic mRNAs

Regulation of Translation during Viral Infection

Inhibition of Translation Initiation after Viral Infection

Regulation of eIF4F

Regulation of Poly(A)-Binding Protein Activity

Regulation of eIF3

Interfering with RNA

Stress-Associated RNA Granules

Perspectives

References

Study Questions

12 Intracellular Trafficking

Introduction

Assembly within the Nucleus

Import of Viral Proteins for Assembly

Assembly at the Plasma Membrane

Transport of Viral Membrane Proteins to the Plasma Membrane

Sorting of Viral Proteins in Polarized Cells

Disruption of the Secretory Pathway in Virus-Infected Cells

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

Interactions with Internal Cellular Membranes

Localization of Viral Proteins to Compartments of the Secretory Pathway

Localization of Viral Proteins to the Nuclear Membrane

Transport of Viral Genomes to Assembly Sites

Transport of Genomic and Pregenomic RNA from the Nucleus to the Cytoplasm

Transport of Genomes from the Cytoplasm to the Plasma Membrane

Perspectives

References

Study Questions

13 Assembly, Release, and Maturation

Introduction

Methods of Studying Virus Assembly and Egress

Structural Studies of Virus Particles

Visualization of Assembly and Exit by Microscopy

Biochemical and Genetic Analyses of Assembly Intermediates

Methods Based on Recombinant DNA Technology

Assembly of Protein Shells

Formation of Structural Units

Capsid and Nucleocapsid Assembly

Self-Assembly and Assisted Assembly Reactions

Selective Packaging of the Viral Genome and Other Components of Virus Particles

Concerted or Sequential Assembly

Recognition and Packaging of the Nucleic Acid Genome

Incorporation of Enzymes and Other Nonstructural Proteins

Acquisition of an Envelope

Sequential Assembly of Internal Components and Budding from a Cellular Membrane

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

Release of Virus Particles

Assembly and Budding at the Plasma Membrane

Assembly at Internal Membranes: the Problem of Exocytosis

Release of Nonenveloped Virus Particles

Maturation of Progeny Virus Particles

Proteolytic Processing of Structural Proteins

Other Maturation Reactions

Cell-to-Cell Spread

Perspectives

References

Study Questions

14 The Infected Cell

Introduction

Signal Transduction

Signaling Pathways

Signaling in Virus-Infected Cells

Gene Expression

Inhibition of Cellular Gene Expression

Differential Regulation of Cellular Gene Expression

Metabolism

Methods To Study Metabolism

Glucose Metabolism

The Citric Acid Cycle

Electron Transport and Oxidative Phosphorylation

Lipid Metabolism

Remodeling of Cellular Organelles

The Nucleus

The Cytoplasm

Perspectives

References

Study Questions

APPENDIX Structure, Genome Organization, and Infectious Cycles of Viruses Featured in this Book

Glossary

Index

Volume 2

Preface

Acknowledgments

About the Authors

1 Infections of Populations: History and Epidemiology

Introduction to Viral Pathogenesis

A Brief History of Viral Pathogenesis

The Relationships among Microbes and the Diseases They Cause

The First Human Viruses Identified and the Role of Serendipity

New Methods Facilitate the Study of Viruses as Causes of Disease

Viral Epidemics in History

Epidemics Shaped History: the 1793 Yellow Fever Epidemic in Philadelphia

Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere

Zoonotic Infections and Epidemics Caused by \"New\" Viruses

The Economic Toll of Viral Epidemics in Livestock

Population Density and World Travel Are Accelerators of Viral Transmission

Focus on Frontline Health Care: Ebolavirus in Africa

Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil

Epidemiology

Fundamental Concepts

Methods Used by Epidemiologists

Surveillance

Network Theory and Practical Applications

Parameters That Govern the Ability of a Virus to Infect a Population

Geography and Population Density

Climate

Perspectives

References

Study Questions

2 Barriers to Infection

Introduction

An Overview of Infection and Immunity

A Game of Chess Played by Masters

Initiating an Infection

Successful Infections Must Modulate or Bypass Host Defenses

Skin

Respiratory Tract

Alimentary Tract

Eyes

Urogenital Tract

Placenta

Viral Tropism

Accessibility of Viral Receptors

Other Host-Virus Interactions That Regulate the Infectious Cycle

Spread throughout the Host

Hematogenous Spread

Neural Spread

Organ Invasion

Entry into Organs with Sinusoids

Entry into Organs That Lack Sinusoids

Organs with Dense Basement Membranes

Skin

Shedding of Virus Particles

Respiratory Secretions

Saliva

Feces

Blood

Urine

Semen

Milk

Skin Lesions

Tears

Perspectives

References

Study Questions

3 The Early Host Response: Cell Autonomous and Innate Immunity

Introduction

The First Critical Moments: How Do Individual Cells Detect a Virus Infection?

Cell Signaling Induced by Viral Entry Receptor Engagement

Receptor-Mediated Recognition of Microbe-Associated Molecular Patterns

Cell Intrinsic Defenses

Apoptosis (Programmed Cell Death)

Necroptosis and Other Cell Death Pathways

Autophagy

Epigenetic Silencing

Cellular Restriction Factors

RNA Interference

CRISPR

The Continuum Between Intrinsic and Innate Immunity

Secreted Immune Mediators of the Innate Immune Response

Overview of Cytokine Functions

Interferons, Cytokines of Early Warning and Action

Chemokines

The Innate Immune Response

Monocytes/macrophages

Complement

Natural Killer Cells

Innate Lymphoid Cells

Other Innate Immune Cells of Relevance to Viral Infections

Perspectives

References

Study Questions

4 Adaptive Immunity and the Establishment of Memory

Introduction

Attributes of the Host Response

Speed

Diversity and Specificity

Memory

Self-Control

Lymphocyte Development, Diversity, and Activation

The Hematopoietic Stem Cell Lineage

The Two Arms of Adaptive Immunity

The Major Effectors of the Adaptive Response: B and T Cells

Diverse Receptors Impart Antigen Specificity to B and T Cells

Events at the Site of Infection Set the Stage for the Adaptive Response

Acquisition of Viral Proteins by Professional Antigen-Presenting Cells Enables Production of Proinflammatory Cytokines and Establishment of Inflammation

Activated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph Nodes

Antigen Processing and Presentation

Professional Antigen-Presenting Cells Induce Activation via Costimulation

Presentation of Antigens by Class I and Class II MHC Proteins

Lymphocyte Activation Triggers Massive Cell Proliferation

The CTL (Cell-Mediated) Response

CTLs Lyse Virus-Infected Cells

Control of CTL Proliferation

Control of Infection by T Cells without Killing

Rashes and Poxes

The Humoral (Antibody) Response

Antibodies Are Made by Plasma Cells

Types and Functions of Antibodies

Virus Neutralization by Antibodies

Antibody-Dependent Cell-Mediated Cytotoxicity: Specific Killing by Nonspecific Cells

Immunological Memory

Perspectives

References

Study Questions

5 Patterns and Pathogenesis

Introduction

Animal Models of Human Diseases

Patterns of Infection

Incubation Periods

Mathematics of Growth Correlate with Patterns of Infection

Acute Infections

Persistent Infections

Latent Infections

Abortive Infections

Transforming Infections

Viral Virulence

Measuring Viral Virulence

Alteration of Viral Virulence

Viral Virulence Genes

Pathogenesis

Infected Cell Lysis

Immunopathology

Immunosuppression Induced by Viral Infection

Oncogenesis

Molecular Mimicry

Perspectives

References

Study Questions

6 Cellular Transformation and Oncogenesis

Introduction

Properties of Transformed Cells

Control of Cell Proliferation

Oncogenic Viruses

Discovery of Oncogenic Viruses

Viral Genetic Information in Transformed Cells

The Origin and Nature of Viral Transforming Genes

Functions of Viral Transforming Proteins

Activation of Cellular Signal Transduction Pathways by Viral Transforming Proteins

Viral Signaling Molecules Acquired from the Cell

Alteration of the Production or Activity of Cellular Signal Transduction Proteins

Disruption of Cell Cycle Control Pathways by Viral Transforming Proteins

Abrogation of Restriction Point Control Exerted by the RB Protein

Production of Virus-Specific Cyclins

Inactivation of Cyclin-Dependent Kinase Inhibitors

Transformed Cells Increase in Size and Survive

Mechanisms That Permit Survival of Transformed Cells

Tumorigenesis Requires Additional Changes in the Properties of Transformed Cells

Inhibition of Immune Defenses

Other Mechanisms of Transformation and Oncogenesis by Human Tumor Viruses

Nontransducing Oncogenic Retroviruses: Tumorigenesis with Very Long Latency

Oncogenesis by Hepatitis Viruses

Perspectives

References

Study Questions

7 Vaccines

Introduction

The Origins of Vaccination

Smallpox: a Historical Perspective

Worldwide Vaccination Programs Can Be Dramatically Effective

Vaccine Basics

Immunization Can Be Active or Passive

Active Vaccination Strategies Stimulate Immune Memory

The Fundamental Challenge

The Science and Art of Making Vaccines

Inactivated Virus Vaccines

Attenuated Virus Vaccines

Subunit Vaccines

Virus-Like Particles

Nucleic Acid Vaccines

Vaccine Technology: Delivery and Improving Antigenicity

Adjuvants Stimulate an Immune Response

Delivery and Formulation

Immunotherapy

The Ongoing Quest for an AIDS Vaccine

Perspectives

References

Study Question Puzzle

8 Antiviral Drugs

 Introduction

A Brief History of Antiviral Drug Discovery

Discovering Antiviral Compounds

The Lexicon of Antiviral Discovery

Screening for Antiviral Compounds

Computational Approaches to Drug Discovery

The Difference between \"R\" and \"D\"

Drug Resistance

Examples of Antiviral Drugs

Inhibitors of Virus Attachment and Entry

Inhibitors of Viral Nucleic Acid Synthesis

Inhibition of Viral Polyprotein Processing and Assembly

Inhibition of Virus Particle Release

Expanding Targets for Antiviral Drug Development

Attachment and Entry Inhibitors

Nucleic Acid-Based Approaches

Proteases and Nucleic Acid Synthesis and Processing Enzymes

Virus Particle Assembly

Microbicides

Two Stories of Antiviral Success

Combination Therapy

Challenges Remaining

Perspectives

References

Study Questions

9 Therapeutic Viruses

 Introduction

Phage Therapy

  History

  Some Advantages and Limitations of Phage Therapy

  Applications in the Clinic and for Disease Prevention

  Future Prospects

Oncolytic Animal Viruses

  From Anecdotal Reports to Controlled Clinical Trials

  Rational Design of Oncolytic Viruses

  Two Clinically Approved Oncolytic Viruses

  Future Directions

Gene Therapy

  Introduction

  Retroviral Vectors

  Adenovirus-Associated Virus Vectors

  Future Prospects

Vaccine Vectors

  DNA Viruses

  RNA Viruses

Perspectives

References

Study Questions

10 Virus Evolution

Virus Evolution

How Do Virus Populations Evolve?

Two General Virus Survival Strategies Can Be Distinguished

Large Numbers of Viral Progeny and Mutants Are Produced in Infected Cells

The Quasispecies Concept

Genetic Shift and Genetic Drift

Fundamental Properties of Viruses That Constrain Evolution

Two General Pathways for Virus Evolution

Evolution of Virulence

The Origin of Viruses

When and How Did They Arise?

Evolution of Contemporary Eukaryotic Viruses

Host-Virus Relationships Drive Evolution

DNA Virus-Host Relationships

RNA Virus-Host Relationships

The Host-Virus \"Arms Race\"

Lessons from Paleovirology

Endogenous Retroviruses

DNA Fossils Derived from Other RNA Viral Genomes

Endogenous Sequences from DNA Viruses

Short- versus Long-Term Rates of Viral Evolution

Perspectives

References

Study Questions

11 Emergence

 The Spectrum