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Shors, Teri. Understanding Viruses, Jones & Bartlett Learning, LLC, 2016.

Brief Contents

CHAPTER 1 Introduction to Viruses

CHAPTER 2 Virus architecture and Nomenclature

CHAPTER 3 Eucaryotic Molecular Biology, Cellular Hurdles, and How Viruses Hijack Host Cells

CHAPTER 4 Mechanisms of Viral entry and Spread of Infection in the Body

CHAPTER 5 Host resistance to Viral Infections

CHAPTER 6 Epidemiology

CHAPTER 7 Laboratory Diagnosis of Viral Diseases and Working with Viruses in the Research Laboratory

CHAPTER 8 Poliovirus and Other Enteroviruses

CHAPTER 9 Influenza Viruses

CHAPTER 10 Hepatitis Viruses

CHAPTER 11 Herpesviruses

CHAPTER 12 Human Immunodeficiency Virus (HIV)

CHAPTER 13 Rabies

CHAPTER 14 Poxviruses

CHAPTER 15 New and Reemerging Viruses

CHAPTER 16 Viruses and Cancer

CHAPTER 17 The History of Medicine, Clinical Trials, Gene Therapy, and Xenotransplantation

Shors,

Contents

Foreword

Preface

Acknowledgements

1 Introduction to Viruses

1.1 Characteristics of Viruses

1.2 Early Virus Studies

1.3 Learning from Viruses

1.4 Theories of Viral Origin

1.5 The Helpful or Collaborative Viruses

1.6 Human and Aquatic Viromes

1.7 Applications of Viruses in Health or Medicine

1.8 Viral Infections: A Brief Introduction to Transmission and Pathogenesis

1.9 Viruses in History: Great Epidemics

1.10 Recent Viral Outbreaks

Summary Resources

2 Virus Architecture and Nomenclature

2.1 Discovery of Emerging Viruses in the 21st Century

2.2 Properties of Viruses

2.3 Viral Structure and Morphology

2.4 Viruses That Challenge the Definition of a Virus

2.5 Taxonomy: What’s in a Name?

2.6 Baltimore Classification

2.7 Viral Disease Syndromes Overlap

Summary

Resources

3 Eucaryotic Molecular Biology, Cellular hurdles, and how Viruses hijack host Cells

3.1 Genes Required for Assembly of Infectious Virus Particles

3.2 Molecular Biology Review

3.3 Molecular Hurdles of the Host Cell

3.4 Virus Replication Cycles: One-Step Growth Curves

3.5 Key Steps of the Viral Replication Cycle

3.6 The Error-Prone RNA Polymerases: Genetic Diversity

3.7 Targets for Antiviral Therapies

Summary Resources

4 Mechanisms of Viral Entry and Spread of Infection in the Body

4.1 Preferred Routes of Entry

4.2 Mechanisms of Viral Spread or Pathogenesis

4.3 Patterns of Diseases

4.4 Virus Exit: Shedding

4.5 Survival of Viruses in the Environment

4.6 Human Viruses in Water Environments

Summary Resources

5 Host Resistance to Viral Infections

5.1 Physiological Factors and Barriers Affecting Resistance

5.2 Host Defenses Against Viral Invaders: Nonspecific Host Defenses (Innate Immunity)

5.3 Immunity Takes Time: Specific Immune System Responses (Adaptive Immunity)

8.2 The History of Polio

8.3 Clinical Features of Poliomyelitis

8.4 Classification and Structure of Poliovirus

8.5 Laboratory Diagnosis of Poliovirus Infections

8.6 Cellular Pathogenesis

8.7 Poliovirus Replication

8.8 Treatments

8.9 Prevention

8.10 Poliovirus Eradication Is Unfinished Business

8.11 Other Enteroviruses (Nonpolio Viruses)

Summary Resources

9 Influenza Viruses

9.1 History of Influenza

9.2 Epidemiology of Influenza

9.3 Clinical Features of Influenza

9.4 Classification of Influenza Viruses

9.5 Laboratory Diagnosis of Influenza

9.6 Cellular Pathogenesis

9.7 Immunity

9.8 Influenza A Virus Replication

9.9 Genetic Variation in Influenza Viruses

9.10 Influenza Pandemics in History

9.11 Influenza Pandemic Scares

9.12 Antivirals for Influenza Treatment

9.13 Vaccines

9.14 International Influenza Surveillance

Summary Resources

10 Hepatitis Viruses

10.1 The History of Viral Hepatitis

10.2 Epidemiology of Viral Hepatitis

10.3 Clinical Features of Viruses That Cause Primary Hepatitis

10.4 Laboratory Diagnosis of Viral Hepatitis Infections

10.5 Hepatitis Virus Replication Cycles

10.6 Pathophysiology of Chronic Hepatitis Virus Infections

10.7 Genetic Diversity of Hepatitis Viruses

10.8 Management and Prevention of Hepatitis A–E Viruses

Summary Resources

11 Herpesviruses

11.1 Herpesvirus History and Nomenclature

11.2 Clinical Signs and Symptoms of Human Herpesviruses

11.3 Laboratory Diagnosis of Herpesvirus Infections

11.4 Herpesvirus Replication Cycle

11.5 Antivirals/Treatment of Herpesvirus Infections

11.6 Chickenpox and the Development of Other Herpesvirus Vaccines

11.7 The Use of Genetically Engineered Herpes Simplex Virus to Treat Brain Tumors

Summary Resources

12 Human Immunodeficiency Virus (HIV)

12.1 The History of HIV

12.2 HIV Transmission

12.3 Prevention of HIV Infection

12.4 Global Epidemiology of HIV/AIDS: Closing the Gap

12.5 HIV/AIDS in Sub-Saharan Africa

12.6 Central Asia and Eastern Europe: Hot Spots in the Worldwide HIV Epidemic

12.7 HIV/AIDS in India and China

12.8 HIV/AIDS in the United States and Six U.S.–Dependent Areas

12.9 Clinical Symptoms of HIV/AIDS

12.10 Laboratory Diagnosis of HIV

12.11 HIV Replication Cycle

12.12 HIV Human Genetics/Resistance: The Smallpox Hypothesis

12.13 Managing HIV Patients: Antiretroviral Therapy (ART)

12.14 HIV and ART-Related Costs in the United States

12.15 Is an HIV Vaccine Possible?

Summary Resources

13 Rabies

13.1 History of Rabies

13.2 Epidemiology of Rabies

13.3 Human Rabies

13.4 Management of Human Rabies

13.5 The Rabies Virus Replication Cycle

13.6 Genetic Variation in Rabies Virus

Summary Resources

14 Poxviruses

14.1 History of Poxviruses

14.2 Clinical Features of Human Poxviruses

14.3 Laboratory Diagnosis of Poxvirus Infections

14.4 Cellular Pathogenesis

16.6 Animal DNA Tumor Viruses

16.7 Oncolytic Viruses

Summary Resources

17 The History of Medicine, Clinical Trials, Gene Therapy, and Xenotransplantation

17.1 Why Is the History of Medicine Important?

17.2 Clinical Trials Today

17.3 Xenotransplantation and the History of Organ Transplants

17.4 Organs: Supply and Demand

17.5 Xenozoonosis

Summary Resources

18 Infectious Molecules: prions and Viroids

18.1 The “Mad” Diseases, Transmissible Spongiform Encephalopathies: Kuru and Cannibalism

18.2 Characteristics and Formation of Infectious Prions

18.3 Oral Transmission: How Do “Eaten” Prions Travel to the Brain to Cause Disease?

18.4 Other Routes of Transmission: Iatrogenic Transmission, Including Prions in Blood

18.5 Clinical Signs and Symptoms of Variant CJD

18.6 Diagnosis of Variant CJD

18.7 Pathogenesis of TSEs

18.8 The PRNP Gene

18.9 Steps Toward Treatment and Vaccination

18.10 Species Barrier: BSE and Variant CJD

18.11 Chronic Wasting Disease

Summary Resources

19 plant Viruses

19.1 History of Plant Viruses

19.2 Transmission of Plant Viruses

19.3 Symptoms of Plant Diseases Caused by Viruses

19.4 Diagnosis and Detection of Plant Viruses

19.5 Prevention and Control of Plant Virus Diseases

19.6 Morphology of Plant Viruses

19.7 Types of Plant Virus Genomes

19.8 Plant Virus Replication Cycles

19.9 Plant Satellite Viruses and Satellite Nucleic Acids

19.10 Plants and RNA Silencing: Plants Possess an Immune System of Their Genomes

19.11 Tobacco Mosaic Virus

19.12 Cassava Viruses

19.13 Citrus Tristeza Virus

19.14 The Next Target: Anticrop Bioterrorism

Summary Resources

20 the Best for Last: Bacteriophages

20.1 History of Bacteriophage Research

20.2 Bacteriophage Ecology

20.3 The Biology of Bacteriophages: Composition and Structure

20.4 Overview of Bacteriophage Infection

20.5 Bacteriophages Create Pathogenic Bacteria in Nature

20.6 Control of Bacteriophages in Industrial Fermentation

20.7 Biofilms and Bacteriophages

20.8 FDA-Approved Listeria-Specific Bacteriophage Preparations

Summary

Resources

A properties of human Viruses

B Baltimore Virus Classification

C Case Study: Combating the Worst epidemic of ebola Virus Disease in human history

Patient Zero

Challenges of an Ebola Epidemic in West Africa Public Health Emergency and the Global Ebola Response

The 6-Month Mark: Scaling Up the Response Case Study Questions

Resources

Glossary

Index

Index of Boxes

Chapter 1

Case Study 1: Viral Hemorrhagic Septicemia: A Major Threat to Fish

Virus File 1-1: Use of PubMed, ScienceDirect, CDC Publications, ProMED-mail, and HealthMap to Research Specific Viruses or to Monitor Viral Outbreaks

Virus File 1-2: “Now I Take My Pen in Hand …”: Letters by a Wisconsin Soldier During

Virus File 4-1: Rabies Transmission: Human Rabies Caused by Tiny Bat Bites

Virus File 4-2: Isolated Reminders of 19th-Century Smallpox Epidemics in America

Virus File 4-3: Is Groundwater Safe to Drink?

Case Study 2: Disturbing Cow Patties

Case Study 3: Screening Travelers for SARS-CoV Infection at Airports

Case Study 4: A Multidrug-Resistant Strain of HIV

Case Study 5: A Reemerging Adenovirus That Causes Severe Illness

Case Study 6: The Rabid Batman Tragedy

Case Study 7: A Smallpox Biohazard?

Chapter 5

Case Study 1: Surviving Ebola Virus Disease

Virus File 5-1: The Massie Puzzle Piece Hiding on Chromosome 6

Refresher: Immunology

Virus File 5-2: Wakefield’s Syndrome (“Autistic Enterocolitis”) and the MMR Vaccination Scare

Case Study 2: Lymphocytic Choriomeningitis Virus: A Virus from Cute Pet Rodents

Case Study 3: Measles in College Chapter 6

Case Study 1: Virus Cold Cases: Brainerd Diarrhea, Sweating Sickness, and Picardy Sweat

Virus File 6-1: Impact of Viruses on War and Religion

Virus File 6-2: Descriptive Epidemiology and AIDS

Virus File 6-3: Sentinel Chicken Surveillance Programs

Virus File 6-4: Today’s Virus Hunters: C. J. Peters and W. Ian Lipkin

Virus File 6-5: Voluntary Quarantine and the Village of Eyam

Case Study 2: Viral Gastroenteritis Linked to Swimming Pool

Case Study 3: Musicians and Viral Infections

Case Study 4: Yellow Fever Virus During a Vacation to Brazil

Chapter 7

Case Study 1: Cluster of Viral Meningitis and Encephalitis Cases

Refresher: PCR

Refresher: Immunology Terms

Virus File 7-1: Diagnosis of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) Caused by Novel Coronaviruses

Virus File 7-2: Development of a Rapid Test to Determine Whether Respiratory Illnesses Are Caused by a Virus or Bacterium

Refresher: Restriction Enzymes

Case Study 2: Severe Brain Infections in Africa and Vietnam Associated with a New Mysterious Cyclovirus

Chapter 8

Case Study 1: Poliomyelitis and Measles in the Amish Community

ViruS File 8-1: Creating Poliovirus in a Test Tube

ViruS File 8-2: Using Google Earth to Track Poliovirus down the Congo River

Case Study 2: Echovirus 4

Chapter 9

Case Study 1: Commingling of Humans, Pigs, and Variant Influenza Viruses at U.S. County Fairs

Virus File 9-1: Retrospective Study Examining the Impact of the 1918 Influenza Pandemic on a Wisconsin Community

Virus File 9-2: The Perfect Storm of Cytokines That Can Kill You

Virus File 9-3: Using Plasmid-Based Reverse Genetics to Produce Avian Influenza A (H5N1) Vaccines

Case Study 2: Human Avian Influenza

Case Study 3: Influenza Diagnostics

Case Study 4: Seasonal Influenza Vaccines

Case Study 5: Avian Influenza on U.S. Poultry Farms

Case Study 6: Sick Dogs and Cats

Chapter 10

Case Study 1: Contaminated Oranges for Tourists in Egypt

Virus File 10-1: Human Viruses Lurking in PortaPotties and Outhouses

Virus File 13-1: Why Did Jeanna Giese Survive?

Case Study 2: A Rabid Cow Named Millie

Case Study 3: Texas Teen Rabies Case

Case Study 4: Rabid Dogs in China

Chapter 14

Case Study 1: Squirrelpox

Virus File 14-1: Deliberate Use of Myxoma Poxviruses to Control Australian Wild Rabbits

Virus File 14-2: Farmer Jesty and the Importance of Self-Promotion

Case Study 2: Smallpox Vaccination

Case Study 3: An Envelope of Smallpox Scabs

Case Study 4: Laboratory-Acquired Cowpox

Chapter 15

Case Study 1: Post-Ebola Syndrome?

Virus File 15-1: Brain-Shrinking Zika Virus Bound for the United States?

Virus File 15-2: Retroviruses Crossing the Species Barrier in Nature: Hunters in Africa Infected with Retroviruses Through Bushmeat

Virus File 15-3: Human Bocavirus (HBoV): An Emerging Viral Pathogen?

Case Study 2: Sick Horses

Case Study 3: Borna Disease

Case Study 4: Mysterious Pig Mortalities

Case Study 5: Puzzling Illness Among Colorado Field Workers

Case Study 6: Baffling Respiratory Distress in Pigs

Chapter 16

Case Study 1: Dr. Dock’s 1896–1897 Observations of Cancer Remission After “Bout with Influenza”

Virus File 16-1: Cell Cycle and Cancer Biology Definitions

Virus File 16-2: Alien DNA and Schizophrenia

Virus File 16-3: The Pap Test Controversy: Papanicolaou vs. Babes

Virus File 16-4: Covered in Warts, “Tree Man” Dies of Rare Disease

Virus File 16-5: Mouth and Throat Cancer and Oral Sex

Virus File 16-6: The SV-40 Controversy: Passenger or Emerging Pathogen? Will SV-40 Large T Antigen Vaccination Become Routine?

Case Study 2: Mysterious Hepatitis Symptoms

Case Study 3: Virotherapy in the Movies

Case Study 4: Infectobesity

Chapter 17

Case Study 1: Can a Shot of Poliovirus Cure Cancer?

Virus File 17-1: Eight Years HIV-Free: Timothy Ray Brown Cured

Virus File 17-2: Rabies Transmission from SolidOrgan Transplants

Case Study 2: Xenozoonosis

Case Study 3: Gene Therapy

Case Study 4: Using Gene Therapy to Treat Cancer

Chapter 18

Case Study 1: Mysterious Illness in a Cat Owner

Virus File 18-1: Point–Counterpoint: Is Spiroplasma Involved in TSEs? The Scientific Debate

Case Study 2: CJD-Like Illness Among Consumers of Squirrel Brains

Case Study 3: CJD-Like Illness Among Deer Hunters

Case Study 4: Human-to-Human CJD Transmission

Case Study 5: Decontaminated Surgical Instruments

Chapter 19

Case Study 1: Plum Pox

Virus File 19-1: Silencing Genes

Chapter 20

Case Study 1: Phage Therapy Resuscitated

Virus File 20-1: Bacteriophage Therapy Makes a Comeback

through comprehensive disease surveillance systems is a key factor in responding to these epidemics. We must also keep focused on the transmission of infectious diseases at the human–animal interface, because so many current diseases are zoonoses, diseases transmitted between humans and animals. This is why a “one health approach” to reducing infectious diseases, where humans and animals are seen as one “contiguous population,” is critical.

The threat of new pandemics fosters innovation and opportunities for collaboration and sharing, among countries and across governments. Global health is driving interdisciplinary approaches in education, requiring students to synthesize, evaluate, and apply knowledge relevant to complex real-world challenges, such as emerging viruses that are contributors to the rise of infectious disease outbreaks. Embracing global health through undergraduate liberal arts programs in education makes it possible for students to connect classroom learning to field testing of solutions. Students who are encouraged to think creatively and holistically about global health challenges may foster a culture of reciprocity.

© Bloomberg/Getty Images.

Michael T. Osterholm, PhD, MPH

Regents Professor

McKnight Endowed Presidential Chair in Public Health Director, Center for Infectious Disease Research and Policy

Distinguished University Teaching Professor

Environmental Health Sciences, School of Public Health Professor, Technological Leadership Institute College of Science and Engineering

Adjunct Professor, Medical School http://www.cidrap.umn.edu

Preface

This third edition of Understanding Viruses is the product of nearly 20 years of teaching introductory virology to undergraduate students majoring in biology, microbiology, and medical technology and to premed and other preprofessional students. Because many of the students in my courses had not taken a micro-biology or cellular and molecular biology course, I found that they lacked knowledge about the fundamental concepts of cell biology and needed some form of “refresher” to aid them through the course material. It was a struggle to find a textbook that combined a holistic approach to understanding viral diseases. Most virology textbooks are focused on the pathogenesis/clinical aspect of viral diseases or the molecular biology of viral replication. Students were more enthusiastic to learn the molecular aspects of viral diseases if the historical and clinical perspectives were presented with it. Understanding Viruses, Third Edition uses an interdisciplinary approach by covering the historical perspectives along with the molecular biology of virus structure and replication, pathobiology (the observed nature of disease, its causes, processes, development, and consequences), and epidemiological impact of viral diseases on local and global populations.

Virology is a dynamic discipline. Emerging viral diseases such as the 2014–2015 Ebola epidemic in West Africa; the spread of Zika virus infections to Brazil in 2015, which was associated with microcephaly in newborns; the threat of pandemic avian influenza A viruses; the spread of Chikungunya virus infections to the Americas in 2013; the impact of global climate change on infectious disease (e.g. insect vectors); the need for the development of new vaccines and antivirals to combat viral diseases; and new cancer therapies

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