Principles of Virology

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

• ISBN13: 9781555811273
• ISBN10: 1555811272
• Format: Hardcover
• Copyright: 1999-11-01
• Publisher: Amer Society for Microbiology

Summary

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.

Table of Contents

Acknowledgments	xix
Organization of This Book	xxiii
I The Science of Virology	1	(56)
Foundations of Virology	2	(22)
Luria's Credo	3	(1)
Virus Prehistory	3	(5)
Viral Infections in Antiquity	3	(1)
The First Vaccines	4	(2)
Microorganisms as Pathogenic Agents	6	(2)
The Discovery of Viruses	8	(3)
The First Viruses	8	(2)
Identification of Human Viruses	10	(1)
The Definitive Properties of Viruses	11	(4)
The Structural Simplicity of Viruses	11	(1)
The Intracellular Parasitism of Viruses	11	(4)
Viruses Defined	15	(1)
Cataloging of Diverse Animal Viruses	16	(4)
Many Sizes and Shapes Produced by Evolution	16	(3)
Genetic Content	19	(1)
Capsid Symmetry	19	(1)
Enveloped or Naked Particles	20	(1)
Virion Enzymes	20	(1)
Unifying Principles	20	(1)
A Common Strategy	20	(1)
Highlights of Virus Strategies Outlined in This Book	21	(1)
References	21	(3)
Virus Cultivation, Detection, and Genetics	24	(33)
Introduction	25	(1)
Cultivation of Viruses	25	(4)
Cell Culture	25	(2)
Embryonated Eggs	27	(1)
Laboratory Animals	28	(1)
Detection of Viruses in the Host	29	(13)
Measurement of Infectious Units	29	(4)
Measurement of Virus Particles and Their Components	33	(7)
The One-Step Growth Cycle	40	(2)
Genetic Analysis of Viruses	42	(13)
Classical Genetic Methods	42	(2)
Engineering Mutations into Viruses	44	(7)
Engineering Viral Genomes: Viral Vectors	51	(4)
Perspectives	55	(1)
References	55	(2)
II Molecular Biology	57	(420)
Virus Structure	58	(42)
Introduction	59	(6)
Functions of the Virion	59	(1)
Nomenclature	60	(2)
Methods for Studying Virus Structure	62	(3)
Building a Protective Coat	65	(22)
Helical Structures	66	(1)
Capsids or Nucleocapsids with Icosahedral Symmetry	66	(18)
Complex Viruses	84	(3)
Packaging the Nucleic Acid Genome	87	(2)
Direct Contact of the Genome with Proteins of the Outer Shell	87	(1)
Packaging by Specialized Virion Proteins	88	(1)
Packaging by Cellular Proteins	88	(1)
Viruses with Envelopes	89	(5)
Viral Envelope Components	90	(2)
Simple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or Nucleocapsid	92	(1)
Enveloped Viruses with Additional Protein Layers	92	(2)
Other Components of Virions	94	(2)
Virion Enzymes	94	(1)
Other Viral Proteins	95	(1)
Cellular Macromolecules	96	(1)
Perspectives	96	(1)
References	97	(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