Principles of Virology, Volume 2: Pathogenesis and Control

ISBN-13: 9781683672852 / Angielski / Miękka / 2020 / 528 str.

S. Jane Flint; Vincent R. Racaniello; Glenn F. Rall

Spis treści

Preface xviiAcknowledgments xxiAbout the Authors xxiiiKey of Repetitive Elements xxv1 Infections of Populations: History and Epidemiology 2Introduction to Viral Pathogenesis 3A Brief History of Viral Pathogenesis 4The Relationships among Microbes and the Diseases They Cause 4The First Human Viruses Identified and the Role of Serendipity 5New Methods Facilitate the Study of Viruses as Causes of Disease 7Viral Epidemics in History 8Epidemics Shaped History: the 1793 Yellow Fever Epidemic in Philadelphia 9Tracking Epidemics by Sequencing: West Nile Virus Spread to the Western Hemisphere 10Zoonotic Infections and Epidemics Caused by "New" Viruses 11The Economic Toll of Viral Epidemics in Livestock 12Population Density and World Travel Are Accelerators of Viral Transmission 12Focus on Frontline Health Care: Ebolavirus in Africa 12Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil 13Epidemiology 14Fundamental Concepts 14Methods Used by Epidemiologists 17Surveillance 17Network Theory and Practical Applications 20Parameters That Govern the Ability of a Virus to Infect a Population 20Geography and Population Density 20Climate 23Perspectives 26References 27Study Questions 282 Barriers to Infection 30Introduction 31An Overview of Infection and Immunity 31A Game of Chess Played by Masters 31Initiating an Infection 33Successful Infections Must Modulate or Bypass Host Defenses 34Skin 34Respiratory Tract 35Alimentary Tract 38Eyes 41Urogenital Tract 42Placenta 42Viral Tropism 43Accessibility of Viral Receptors 44Other Host-VirusInteractions That Regulate the Infectious Cycle 44Spread throughout the Host 45Hematogenous Spread 47Neural Spread 50Organ Invasion 51Entry into Organs with Sinusoids 51Entry into Organs That Lack Sinusoids 51Organs with Dense Basement Membranes 53Skin 53Shedding of Virus Particles 54Respiratory Secretions 54Saliva 55Feces 55Blood 56Urine 56Semen 56Milk 56Skin Lesions 56Tears 56Perspectives 57References 58Study Questions 593 The Early Host Response: Cell Autonomous and Innate Immunity 60Introduction 61The First Critical Moments: How Do Individual Cells Detect a Virus Infection? 62Cell Signaling Induced by Viral Entry Receptor Engagement 63Receptor-Mediated Recognition of Microbe-Associated Molecular Patterns 64Cell-Intrinsic Defenses 70Apoptosis (Programmed Cell Death) 70Programmed Necrosis (Necroptosis) 75Autophagy 77Epigenetic Silencing 77Host Proteins That Restrict Virus Reproduction (Restriction Factors) 79RNA Interference 83CRISPR 83The Continuum between Intrinsic and Innate Immunity 83Secreted Mediators of the Innate Immune Response 83Overview of Cytokine Functions 85Interferons, Cytokines of Early Warning and Action 86Chemokines 94The Innate Immune Response 96Monocytes, Macrophages, and Dendritic Cells 97Complement 97Natural Killer Cells 99Other Innate Immune Cells Relevant to Viral Infections 101Perspectives 103References 104Study Questions 1064 Adaptive Immunity and Establishment of Memory 108Introduction 109Attributes of the Host Response 109Speed 109Diversity and Specificity 110Memory 110Self-Control 111Lymphocyte Development, Diversity, and Activation 111The Hematopoietic Stem Cell Lineage 111The Two Arms of Adaptive Immunity 112The Major Effectors of the Adaptive Response: B and T Cells 112Diverse Receptors Impart Antigen Specificity to B and T Cells 118Events at the Site of Infection Set the Stage for the Adaptive Response 120Acquisition of Viral Proteins by Professional Antigen-Presenting Cells Enables Production of Proinflammatory Cytokines and Establishment of Inflammation 120Activated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph Nodes 122Antigen Processing and Presentation 125Professional Antigen-Presenting Cells Induce Activation via Costimulation 125Presentation of Antigens by Class I and Class II MHC Proteins 125Lymphocyte Activation Triggers Massive Cell Proliferation 128The CTL (Cell-Mediated) Response 130CTLs Lyse Virus-Infected Cells 130Control of CTL Proliferation 132Control of Infection by CTLs without Killing 134Rashes and Poxes 134The Humoral (Antibody) Response 136Antibodies Are Made by Plasma Cells 136Types and Functions of Antibodies 137Virus Neutralization by Antibodies 137Antibody-Dependent Cell-Mediated Cytotoxicity: Specific Killing by Nonspecific Cells 140Immunological Memory 140Perspectives 142References 143Study Question Puzzle 1455 Patterns and Pathogenesis 146Introduction 147Animal Models of Human Diseases 147Patterns of Infection 151Incubation Periods 151Mathematics of Growth Correlate with Patterns of Infection 152Acute Infections 152Persistent Infections 155Latent Infections 163Abortive Infections 170Transforming Infections 171Viral Virulence 171Measuring Viral Virulence 171Approaches to Identify Viral Genes That Contribute to Virulence 171Viral Virulence Genes 173Pathogenesis 176Infected Cell Lysis 176Immunopathology 177Immunosuppression Induced by Viral Infection 181Oncogenesis 183Molecular Mimicry 183Perspectives 183References 185Study Question Puzzle 1866 Cellular Transformation and Oncogenesis 188Introduction 189Properties of Transformed Cells 189Control of Cell Proliferation 193Oncogenic Viruses 197Discovery of Oncogenic Viruses 197Viral Genetic Information in Transformed Cells 200The Origin and Nature of Viral Transforming Genes 205Functions of Viral Transforming Proteins 206Activation of Cellular Signal Transduction Pathways by Viral Transforming Proteins 206Viral Signaling Molecules Acquired from the Cell 207Alteration of the Production or Activity of Cellular Signal Transduction Proteins 209Disruption of Cell Cycle Control Pathways by Viral Transforming Proteins 215Abrogation of Restriction Point Control Exerted by the RB Protein 215Production of Virus-Specific Cyclins 218Inactivation of Cyclin-Dependent Kinase Inhibitors 218Transformed Cells Increase in Size and Survive 218Mechanisms That Permit Survival of Transformed Cells 219Tumorigenesis Requires Additional Changes in the Properties of Transformed Cells 221Inhibition of Immune Defenses 222Other Mechanisms of Transformation and Oncogenesis by HumanTumor Viruses 222Nontransducing Oncogenic Retroviruses: Tumorigenesis with Very Long Latency 222Oncogenesis by Hepatitis Viruses 223Perspectives 225References 226Study Questions 2287 Vaccines 230Introduction 231The Origins of Vaccination 231Smallpox: a Historical Perspective 231Worldwide Vaccination Programs Can Be Dramatically Effective 232Vaccine Basics 237Immunization Can Be Active or Passive 237Active Vaccination Strategies Stimulate Immune Memory 238The Fundamental Challenge 243The Science and Art of Making Vaccines 243Inactivated Virus Vaccines 244Attenuated Virus Vaccines 247Subunit Vaccines 250Virus-Like Particles 252Nucleic Acid Vaccines 253Vaccine Technology: Delivery and Improving Antigenicity 254Adjuvants Stimulate an Immune Response 254Delivery and Formulation 254Immunotherapy 255The Ongoing Quest for an AIDS Vaccine 255Perspectives 256References 257Study Question Puzzle 2598 Antiviral Drugs 260Introduction 261A Brief History of Antiviral Drug Discovery 261Discovering Antiviral Compounds 262The Lexicon of Antiviral Discovery 262Screening for Antiviral Compounds 264Computational Approaches to Drug Discovery 266The Difference between "R" and "D" 269Drug Resistance 271Examples of Antiviral Drugs 272Inhibitors of Virus Attachment and Entry 272Inhibitors of Viral Nucleic Acid Synthesis 275Inhibition of Viral Polyprotein Processing and Assembly 282Inhibition of Virus Particle Release 284Expanding Targets for Antiviral Drug Development 284Attachment and Entry Inhibitors 286Nucleic Acid-Based Approaches 286Proteases and Nucleic Acid Synthesis and Processing Enzymes 287Virus Particle Assembly 287Microbicides 287Two Stories of Antiviral Success 287Combination Therapy 288Challenges Remaining 290Perspectives 291References 294Study Questions 2959 Therapeutic Viruses 296Introduction 297Phage Therapy 297History 297Some Advantages and Limitations of Phage Therapy 298Applications in the Clinic and for Disease Prevention 299Future Prospects 301Oncolytic Animal Viruses 302From Anecdotal Reports to Controlled Clinical Trials 302Rational Design of Oncolytic Viruses 304Two Clinically Approved Oncolytic Viruses 307Future Directions 308Gene Therapy 308Introduction 308Retroviral Vectors 309Adenovirus-Associated Virus Vectors 316Future Prospects 321Vaccine Vectors 322DNA Viruses 322RNA Viruses 325Perspectives 328References 330Study Questions 33110 Virus Evolution 332Virus Evolution 333How Do Virus Populations Evolve? 333Two General Virus Survival Strategies Can Be Distinguished 333Large Numbers of Viral Progeny and Mutants Are Produced in Infected Cells 334The Quasispecies Concept 335Genetic Shift and Genetic Drift 338Fundamental Properties of Viruses That Constrain Evolution 339Two General Pathways for Virus Evolution 339Evolution of Virulence 340The Origin of Viruses 342When and How Did They Arise? 342Evolution of Contemporary Eukaryotic Viruses 342Host-Virus Relationships Drive Evolution 348DNA Virus-Host Relationships 348RNA Virus-Host Relationships 350The Host-Virus "Arms Race" 351Lessons from Paleovirology 353Endogenous Retroviruses 353DNA Fossils Derived from Other RNA Viral Genomes 355Endogenous Sequences from DNA Viruses 355Short-versus Long-Term Rates of Viral Evolution 358Perspectives 358References 359Study Questions 36011 Emergence 362The Spectrum of Host-Virus Interactions 363Stable Interactions 363The Evolving Host-Virus Interaction 364The Dead-End Interaction 364The Resistant Host 366Encountering New Hosts: Humans Constantly Provide New Venues for Infection 368Common Sources for Animal-to-Human Transmission 370Viral Diseases That Illustrate the Drivers of Emergence 372Poliomyelitis: Unexpected Consequences of Modern Sanitation 372Introduction of Viruses into Naïve Populations 372Hantavirus Pulmonary Syndrome: Changing Animal Populations 374Severe Acute and Middle East Respiratory Syndromes (SARS and MERS): Zoonotic Coronavirus Infections 374The Contribution to Emergence of Mutation, Recombination, or Reassortment 376Canine Parvoviruses: Cat-to-Dog Host Range Switch by Two Amino Acid Changes 376Influenza Epidemics and Pandemics: Escaping the Immune Response by Reassortment 376New Technologies Uncover Previously Unrecognized Viruses 378Hepatitis Viruses in the Human Blood Supply 378A Revolution in Virus Discovery 380Perceptions and Possibilities 381Virus Names Can Be Misleading 382All Viruses Are Important 382Can We Predict the Next Viral Pandemic? 382Preventing Emerging Virus Infections 383Perspectives 384References 384Study Questions 38512 Human Immunodeficiency Virus Type I Pathogenesis 386Introduction 387Worldwide Impact of AIDS 387HIV-1 Is a Lentivirus 387Discovery and Characterization 387Distinctive Features of the HIV-1 Reproduction Cycle and the Functions of HIV-1 Proteins 390The Viral Capsid Counters Intrinsic Defense Mechanisms 398Entry and Transmission 400Entry in the Cell 400Entry into the Body 401Transmission in Human Populations 402The Course of Infection 403The Acute Phase 403The Asymptomatic Phase 406The Symptomatic Phase and AIDS 406Effects of HIV-1 on Other Tissues and Organs 406Virus Reproduction 408Dynamics in the Absence of Treatment 408Dynamics of Virus Reproduction during Treatment 408Latency 410Immune Responses to HIV-1 411Innate Response 411Humoral Responses 411HIV-1 and Cancer 412Kaposi's Sarcoma 412B-Cell Lymphomas 413Anogenital Carcinomas 413Prospects for Treatment and Prevention 414Antiviral Drugs 414Confronting the Problems of Persistence and Latency 415Gene Therapy Approaches 415Immune System-Based Therapies 417Antiviral Drug Prophylaxis 417Perspectives 417References 418Study Questions 41913 Unusual Infectious Agents 420Introduction 421Viroids 421Replication 421Sequence Diversity 424Movement 424Pathogenesis 425Satellite Viruses and RNAs 425Replication 426Pathogenesis 426Hepatitis Delta Virus 426Prions and Transmissible Spongiform Encephalopathies 427Scrapie 427Physical Properties of the Scrapie Agent 429Human TSEs 429Hallmarks of TSE Pathogenesis 429Prions and the prnp Gene 429Prion Strains 434Bovine Spongiform Encephalopathy 435Chronic Wasting Disease 436Treatment of Prion Diseases 437Perspectives 438References 439Study Questions 439Appendix Epidemiology and Pathogenesis of Selected Human Viruses 441Glossary 471Index 477

O autorze

Jane Flint is Professor Emerita of Molecular Biology at Princeton University. Dr. Flint's research focused on investigation of the mechanisms by which viral gene products modulate host pathways and antiviral defenses to allow efficient reproduction in normal human cells of adenoviruses, viruses that are used in such therapeutic applications as gene transfer and cancer treatment.Vincent R. Racaniello is Higgins Professor of Microbiology & Immunology at Columbia University Vagelos College of Physicians & Surgeons. Dr. Racaniello has been studying viruses for over 40 years, including polio- virus, rhinovirus, enteroviruses, hepatitis C virus, and Zika virus. He blogs about virus-es at virology.ws and is host of This Week in Virology.Glenn F. Rall is a Professor and the Chief Academic Officer at the Fox Chase Cancer Center, and is an Adjunct Professor in the Microbiology and Immunology departments at the University of Pennsylvania, as well as Thomas Jefferson, Drexel, and Temple Universities. Dr. Rall studies viral infections of the brain and the immune responses to those infections, with the goal of defining how viruses contribute to disease.Theodora Hatziioannou is a Research Associate Professor at Rockefeller University and is actively involved in teaching programs at Albert Einstein College of Medicine. Dr. Hatziioannou has worked on multiple viruses with a focus on retroviruses and the molecular mechanisms that govern virus tropism and on the improvement of animal models for human disease.Anna Marie Skalka is a Professor Emerita and former Senior Vice President for Basic Research at the Fox Chase Cancer Center. Dr. Skalka is internationally recognized for her contributions to the understanding of the biochemical mechanisms by which retroviruses replicate and insert their genetic material into the host genome, as well as her research into other molecular aspects of retrovirus biology.