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Chapter 1 ...... 1 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC ChapterNOT 2 Virus FOR ASALErchitecture OR DISTRIBUTION and Nomenclature...... NOT . . . FOR. . . . SALE OR .72DISTRIBUTION Chapter 3  eucaryotic , Cellular Hurdles, and how Viruses Hijack Cells...... 100 Chapter 4 Mechanisms of and Spread of in the Body ...... 156 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOTChapter FOR SALE 5 H ORhost DISTRIBUTION Resistance to Viral . .NOT . . . FOR . . . SALE. . . . OR. . .DISTRIBUTION . . .202 Chapter 6 Epidemiology...... 264 Chapter 7  Laboratory Diagnosis of Viral Diseases and Working with © Jones & Bartlett Learning, LLC Viruses in the Research© Jones Laboratory & Bartlett. . . . .Learning, ...... LLC. . . . .320 NOT FOR SALE ORChapter DISTRIBUTION 8 P and Other EnterovirusesNOT FOR SALE. . . . OR . . DISTRIBUTION...... 361 Chapter 9 Viruses ...... 391 Chapter 10 hepatitis Viruses ...... 453 Chapter© 11 Jones Herpesviruses & Bartlett. .Learning, ...... LLC ...... © . Jones. . . & Bartlett .491Learning, LLC ChapterNOT 12 h FORuman SALE OR DISTRIBUTION Virus H( IV)...... NOT . . . FOR . . . SALE. OR .527 DISTRIBUTION Chapter 13 ...... 584 Chapter 14 Poxviruses...... 616 © JonesChapter & Bartlett 15 New Learning, and Reemerging LLC Viruses. . . . .© . Jones. . . . . & . Bartlett...... Learning, . . LLC .649 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 16 Viruses and Cancer ...... 686 Chapter 17 Tthe History of Medicine, Clinical Trials, Therapy, and Xenotransplantation ...... 744 © Jones & BartlettChapter Learning, 18 LLCInfectious Molecules: P©rions Jones and & Viroids Bartlett. . Learning,...... LLC...... 771 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 19 plant Viruses...... 798 Chapter 20 the Best for Last: ...... 826 Appendix A Properties of Viruses...... 845 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Appendix B Baltimore ...... 848 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Appendix C Case Study: Combating the Worst of Ebola Virus Disease in ...... 850 Glossary ...... 877 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOTind FORex SALE . . . . . OR . . . DISTRIBUTION...... NOT. . . . . FOR. . . . . SALE ...... OR . . . DISTRIBUTION...... 903

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Foreword...... xiii 3.6 The Error-Prone RNA Polymerases: Preface ...... © . .Jones . . . . . &. . Bartlett . . . . Learning, .xiv LLC Genetic Diversity. . .© . Jones. . . . &. Bartlett. . . . . Learning,. 142 LLC Acknowledgements. . NOT. . . . .FOR . . . . SALE . . . . . OR. DISTRIBUTIONxxiii 3.7 Targets for Antiviral TherapiesNOT FOR. . . SALE . . . .OR . .DISTRIBUTION 142 1 Introduction to Viruses...... 1 Summary...... 148 1.1 Characteristics of Viruses ...... 6 Resources ...... 152 1.2 Early© Jones Virus Studies & Bartlett. . . . Learning, ...... LLC . . . . . 6 4 Mechanisms© Jones of Viral& Bartlett Entry and Learning, LLC 1.3 LearningNOT FOR from SALEViruses .OR . . DISTRIBUTION...... 10 SpreadNOT of Infection FOR SALE in the OR Body DISTRIBUTION...... 156 1.4 Theories of Viral Origin ...... 14 4.1 Preferred Routes of Entry...... 159 1.5 The Helpful or Collaborative Viruses...... 20 4.2 Mechanisms of Viral Spread 1.6 Human and Aquatic Viromes ...... 22 or Pathogenesis...... 167 © Jones &1.7 Bartlett Applications Learning, of Viruses LLC in Health or Medicine. . . 26© Jones4.3 &Patterns Bartlett of Diseases Learning,. . . .LLC ...... 180 NOT FOR1.8 SALE Viral Infections:OR DISTRIBUTION A Brief Introduction NOT FOR4.4 Virus SALE Exit: OR Shedding DISTRIBUTION...... 183 to Transmission and Pathogenesis ...... 32 4.5 Survival of Viruses in the Environment...... 184 1.9 Viruses in History: Great ...... 32 4.6 Human Viruses in Water Environments...... 185 1.10 Recent Viral Outbreaks ...... 42 Summary...... 188 Summary...... 60 © Jones & Bartlett Learning, LLCResources ...... ©. .Jones . . . .& . Bartlett . . . . .Learning, .199 LLC Resources ...... NOT . . .FOR . . .SALE . . . OR. . .DISTRIBUTION . . 64 NOT FOR SALE OR DISTRIBUTION 5 host Resistance to Viral Infections...... 202 2 Virus Architecture and Nomenclature...... 72 5.1 Physiological Factors and Barriers 2.1 Discovery of Emerging Viruses in the Affecting Resistance...... 205 21st Century ...... 74 © Jones & Bartlett Learning, LLC 5.2 Host© Def Jonesenses Against & Bartlett Viral Learning, LLC 2.2 PropertiesNOT FOR of VirusesSALE. OR. . .DISTRIBUTION ...... 76 Invaders:NOT Nonspecific FOR SALE Host OR Defenses DISTRIBUTION 2.3 Viral Structure and Morphology...... 78 (Innate ) ...... 212 2.4 Viruses That Challenge the Definition of a Virus. . 82 5.3 Immunity Takes Time: Specific Immune 2.5 Taxonomy: What’s in a Name?...... 87 System Responses (Adaptive Immunity). . . . . 225 5.4 Virus Evasion Strategies ...... 233 © Jones &2.6 Bartlett Baltimore Learning, Classification LLC...... 88© Jones & Bartlett Learning, LLC 5.5 Serum Therapy and ...... 234 NOT FOR2.7 SALE Viral DiseaseOR DISTRIBUTION Syndromes Overlap ...... 93NOT FOR SALE OR DISTRIBUTION Summary...... 94 5.6 ...... 237 Resources ...... 97 Summary...... 255 Resources ...... 260 3 eucaryotic Molecular Biology, Cellular © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Hurdles, and How Viruses Hijack 6 Epidemiology...... 264 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Host Cells...... 100 6.1 What Is Epidemiology?...... 268 3.1 Required for Assembly of 6.2 History of Epidemiology: From Observational Infectious Virus Particles...... 104 Data to Preventative Action ...... 272 3.2 Molecular Biology Review...... 104 6.3 The Complexities of Disease Transmission. . . . 275 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 3.3 Molecular Hurdles of the Host ...... 118 6.4 Epidemiology Today...... 281 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 3.4 Virus Replication Cycles: One-Step 6.5 Prevention and Containment of Growth Curves...... 121 Contagious Diseases ...... 291 3.5 Key Steps of the Cycle. . . . . 123 6.6 Travel Medicine...... 301 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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9781284057898_FMxx_00i_xxiv.indd 5 04/07/16 9:11 am 6.7 Tracking Diseases from Outer 9.13 Vaccines...... 440 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Space: Remote Sensing and Early 9.14 International Influenza Surveillance...... 441 NOT FOR SALEWarning OR Systems DISTRIBUTION...... 311 NOT FOR SALE OR DISTRIBUTION Summary...... 443 Summary...... 312 Resources ...... 448 Resources ...... 316 10 hepatitis Viruses...... 453 7 Laboratory Diagnosis© Jones of Viral & Diseases Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 10.1 The History of ...... 455 and Working with VirusesNOT FOR in the SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Research Laboratory ...... 320 10.2 Epidemiology of Viral Hepatitis...... 459 10.3 Clinical Features of Viruses That Cause 7.1 Proving Causation of Viral Diseases...... 325 Primary Hepatitis...... 463 7.2 Viral Diagnostics in the Clinical Laboratory. . . .326 10.4 Laboratory Diagnosis of Viral 7.3 Viral © Lo Jonesad Testing & Bartlettand Drug Learning, LLC Hepatitis© Jones Infections &. Bartlett. . . . . Learning, ...... LLC . 465 SusceptibilityNOT FOR Testing SALE. . OR. . .DISTRIBUTION ...... 345 10.5 HepatitisNOT Virus FOR Replic SALEation CyclesOR DISTRIBUTION...... 469 7.4 Working with Viruses in the 10.6 Pathophysiology of Chronic Hepatitis Research Laboratory...... 346 Virus Infections...... 478 7.5 Laboratory Safety...... 355 10.7 Genetic Diversity of Hepatitis Viruses...... 478 © JonesSummary & Bartlett. . . Learning,...... LLC...... 356 © Jones10.8 Management & Bartlett and Learning, Prevention LLC of NOT FORResourc SALEes . OR. . .DISTRIBUTION ...... 359 NOT FORHepatitis SALE A–E OR Viruses DISTRIBUTION...... 478 Summary...... 485 8 poliovirus and Other ...... 361 Resources ...... 489 8.1 Brief Overview of Enteroviruses...... 363 8.2 The History of ©. . Jones . . . . & . Bartlett. . . . . Learning, . .364 LLC11 Herpesviruses. . . . .© . .Jones . . . . &. .Bartlett . . 491Learning, LLC 8.3 Clinical Features of PoliomyelitisNOT FOR . SALE. . . .OR . . DISTRIBUTION. 366 11.1 Herpesvirus History andNOT Nomenclat FOR ureSALE. . . OR. .493 DISTRIBUTION 8.4 Classification and Structure of Poliovirus . . . . 369 11.2 Clinical Signs and Symptoms of Human 8.5 Laboratory Diagnosis of Poliovirus Infections. . .370 Herpesviruses...... 496 8.6 Cellular Pathogenesis ...... 370 11.3 Laboratory Diagnosis of 8.7 Poliovirus© Jones Replication & Bartlett. . . Learning,...... LLC. . . .370 Herpesvirus© Jones Infections & Bartlett. . . . .Learning, ...... LLC . 505 8.8 TreatmentsNOT FOR. . .SALE . . . OR. . DISTRIBUTION...... 375 11.4 HerpesvirusNOT ReplicationFOR SALE Cycle OR. . DISTRIBUTION ...... 506 8.9 Prevention...... 375 11.5 Antivirals/T reatment of Herpesvirus Infections...... 510 8.10 Poliovirus Eradication Is Unfinished Business. . 380 11.6 and the Development of 8.11 Other Enteroviruses (Nonpolio Viruses). . . . .383 Other Herpesvirus Vaccines ...... 516 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Summary...... 386 11.7 The Use of Genetically Engineered Herpes NOT FORResourc SALEes . OR. . .DISTRIBUTION ...... 388 NOT FORSimplex SALE Virus OR to DISTRIBUTIONTreat Brain Tumors...... 517 Summary...... 519 9 Influenza Viruses...... 391 Resources ...... 524 9.1 History of Influenza ...... 395 9.2 Epidemiology of Influenz© Jonesa . . . & . Bartlett. . . . . Learning, . .396 LLC12 human Immunodeficiency© Jones Virus & (H IV)Bartlett. . . . . 527Learning, LLC 9.3 Clinical Features of InfluenzaNOT FOR. . .SALE . . . OR. . .DISTRIBUTION .396 12.1 The History of HIV. . . NOT. . . FOR. . . SALE. . . .OR . 532 DISTRIBUTION 9.4 Classification of Influenza Viruses...... 399 12.2 HIV Transmission ...... 537 9.5 Laboratory Diagnosis of Influenza...... 400 12.3 Prevention of HIV Infection...... 540 9.6 Cellular Pathogenesis ...... 401 12.4 Global Epidemiology of HIV/AIDS: Closing 9.7 Immunity© Jones. . .& . Bartlett . . . . .Learning, ...... LLC . . . 402 the Gap©. Jones. . . . &. Bartlett. . . . . Learning,...... LLC. .541 9.8 InfluenzaNOT FOR A Virus SALE Replication OR .DISTRIBUTION ...... 403 12.5 HIV/AIDSNOT in Sub FOR-Saharan SALE Africa OR. DISTRIBUTION...... 543 9.9 Genetic Variation in Influenza Viruses...... 415 12.6 Central Asia and Eastern Europe: Hot Spots 9.10 Influenza in History...... 420 in the Worldwide HIV Epidemic ...... 544 9.11 Influenza Scares...... 432 12.7 HIV/AIDS in India and China...... 545 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 9.12 Antivirals for Influenza Treatment...... 438 12.8 HIV/AIDS in the United States and Six NOT FOR SALE OR DISTRIBUTION NOT FORU.S.–Dependent SALE OR DISTRIBUTION Areas...... 548

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9781284057898_FMxx_00i_xxiv.indd 6 04/07/16 9:11 am 12.9 Clinical Symptoms of HIV/AIDS1...... 556 15.3 Environmental Factors Contributing to New © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 12.10 Laboratory Diagnosis of HIV...... 559 and Reemerging Viral Infections ...... 678 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 12.11 HIV Replication Cycle...... 561 Summary...... 679 12.12 HIV Human Genetics/Resistance: Resources ...... 683 The Hypothesis...... 566 16 Viruses and Cancer...... 686 12.13 Managing HIV Patients: Antiretroviral Therapy (ART). ©. Jones. . . . &. .Bartlett . . . . Learning,. . . 568 LLC16.1 History of Cancer Viruses© Jones and Tumors & Bartlett. . . . Learning,. 689 LLC 12.14 HIV and ART-RelatedNOT Costs FOR in SALE the OR DISTRIBUTION16.2 Cancer Today. . . . NOT. . . FOR. . . SALE. . . .OR . . DISTRIBUTION690 United States...... 574 16.3 Molecular Mechanisms of Virally 12.15 Is an HIV Possible?...... 574 Induced Tumor Formation by RNA Tumor Viruses () ...... 694 Summary...... 574 16.4 Human Retroviruses ...... 700 Resourc© Joneses . . . &. .Bartlett . . . . Learning,...... LLC. . . . .579 © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION 16.5 HumanNOT DNA FOR Tumor SALE Viruses OR. . .DISTRIBUTION ...... 703 13 Rabies...... 584 16.6 Animal DNA Tumor Viruses...... 716 13.1 History of Rabies...... 586 16.7 Oncolytic Viruses ...... 722 13.2 Epidemiology of Rabies...... 587 Summary...... 734 © Jones &13.3 Bartlett Human RabiesLearning,. . . . LLC ...... 592© JonesResourc & Bartlettes . . . . Learning, ...... LLC ...... 741 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 13.4 Management of Human Rabies ...... 602 17 the History of Medicine, Clinical Trials, 13.5 The Replication Cycle...... 605 Gene Therapy, and Xenotransplantation . . . . 744 13.6 Genetic Variation in Rabies Virus...... 608 17.1 Why Is the History of Medicine Important? . . . 747 Summary...... 608 © Jones & Bartlett Learning, LLC17.2 Clinical Trials Today. ©. Jones. . . . &. .Bartlett . . . . Learning,. 754 LLC Resources ...... 613 NOT FOR SALE OR DISTRIBUTION17.3 Xenotransplantation NOTand the FOR History SALE OR DISTRIBUTION of Organ Transplants...... 757 14 Poxviruses...... 616 17.4 Organs: Supply and Demand ...... 758 14.1 History of Poxviruses...... 617 17.5 Xenozoonosis ...... 761 14.2 Clinical Features of Human Poxviruses. . . . . 618 Summary...... 766 14.3 ©Laborator Jonesy &Diagnosis Bartlett of PoxvirusLearning, Infections LLC. . .622 © Jones & Bartlett Learning, LLC Resources ...... 769 14.4 NOTCellular FOR Pathogenesis SALE OR. . .DISTRIBUTION ...... 623 NOT FOR SALE OR DISTRIBUTION 14.5 Naming and Structure of Poxviruses...... 623 18 Infectious Molecules: 14.6 Vaccinia Virus Replication...... 624 and Viroids...... 771 14.7 Poxviruses and Immune Evasion...... 626 18.1 The “Mad” Diseases, Transmissible Spongiform © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 14.8 Human Genetics and Smallpox Resistance . . . 627 Encephalopathies: Kuru and Cannibalism. . . .773 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 14.9 Smallpox Eradication...... 628 18.2 Characteristics and Formation of Infectious Prions...... 774 14.10 Recombinant Vaccinia Viruses as Research Tools and Vaccines ...... 628 18.3 Oral Transmission: How Do “Eaten” Prions Travel to the Brain to Cause Disease?...... 776 14.11 Prevention: Vaccines...... 632 © Jones & Bartlett Learning, LLC18.4 Other Routes of Transmission:© Jones Iatrogenic & Bartlett Learning, LLC 14.12 Antivirals...... 637 NOT FOR SALE OR DISTRIBUTIONTransmission, IncludingNOT Prions FOR in BloodSALE. . OR . . DISTRIBUTION777 14.13 Variola Virus in the Laboratory...... 638 18.5 Clinical Signs and Symptoms of Variant CJD. . .778 14.14 The Variola Destruction Debate...... 639 18.6 Diagnosis of Variant CJD...... 778 14.15 Bioterrorism and Biowarfare...... 639 18.7 Pathogenesis of TSEs...... 778 Summary© Jones. . . .& . Bartlett. . . . .Learning, ...... LLC . . . . 642 18.8 The© PRNP Jones Gene &. . Bartlett. . . . .Learning, ...... LLC . . 779 ResourcNOTes . FOR. . . SALE. . . .OR . . DISTRIBUTION ...... 646 18.9 StepsNOT Toward FOR Treatment SALE andOR Vaccination DISTRIBUTION. . . .780 15 New and Reemerging Viruses...... 649 18.10 Barrier: BSE and Variant CJD. . . . . 781 15.1 Viral and Adaptation ...... 652 18.11 Chronic Wasting Disease...... 782 15.2 Human Factors Contributing to New and 18.12 Plant Viroids ...... 787 © Jones & BartlettReemerging Learning, Viral Infections LLC ...... 654© JonesSummary & Bartlett. . . . Learning,...... LLC...... 792 NOT FOR SALE OR DISTRIBUTION NOT FORResourc SALEes . . OR. . .DISTRIBUTION ...... 795

Contents vii © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 7 04/07/16 9:11 am 19 plant Viruses...... 798 20.4 Overview of Infection...... 833 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 19.1 History of Plant Viruses...... 799 20.5 Bacteriophages Create Pathogenic NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 19.2 Transmission of Plant Viruses...... 800 in Nature ...... 835 19.3 Symptoms of Plant Diseases Caused 20.6 Control of Bacteriophages in Industrial by Viruses...... 802 Fermentation ...... 836 19.4 Diagnosis and Detection of Plant Viruses. . . . 802 20.7 Biofilms and Bacteriophages...... 838 © Jones & Bartlett Learning, LLC20.8 FDA-Appr oved Listeria-Specific© Jones & Bartlett Learning, LLC 19.5 Prevention and ContrNOTol of FOR Plant SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Virus Diseases...... 802 Bacteriophage Preparations...... 840 19.6 Morphology of Plant Viruses...... 803 Summary...... 841 19.7 Types of ...... 803 Resources ...... 843 19.8 Plant© Jones Virus Replication & Bartlett Cycles Learning,. . . . . LLC. . . .805 A properties© Jones of Human & Bartlett Viruses. .Learning, ...... LLC . 845 19.9 PlantNOT FOR VirusesSALE and OR Sat DISTRIBUTIONellite NOT FOR SALE OR DISTRIBUTION Nucleic Acids...... 806 B Baltimore Virus Classification...... 848 19.10 Plants and RNA Silencing: Plants Possess an of Their Genomes . . . . .809 C Case Study: Combating the Worst Epidemic 19.11 ...... 812 of Ebola Virus Disease in Human History . . . . 850 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 19.12 Cassava Viruses...... 816 Patient Zero...... 850 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 19.13 Citrus Tristeza Virus...... 819 Challenges of an Ebola Epidemic in West Africa. . . .851 19.14 The Next Target: Anticrop Bioterrorism. . . . 820 Public Health Emergency and the Global Summary...... 822 Ebola Response ...... 856 The 6-Month Mark: Scaling Up the Response . . . . .863 Resources ...... © . Jones . . . . & . Bartlett. . . . . Learning, . .823 LLC © Jones & Bartlett Learning, LLC Case Study Questions...... 869 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 20 the Best for Last: Bacteriophages...... 826 Resources ...... 873 20.1 History of Bacteriophage Research...... 827 20.2 Bacteriophage Ecology...... 832 Glossary...... 877 20.3 The Biology of Bacteriophages: Composition Index...... 903 and© StructureJones &. .Bartlett . . . . .Learning, ...... LLC . . . 832 © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Index of Boxes

© Jones & Bartlett Learning, LLC Chapter© Jones 1 & Bartlett Learning, LLC NOT FORCase SALE Study OR1: Viral DISTRIBUTION Hemorrhagic Septicemia: A Major ThreatNOT to FOR Fish . SALE. . . . .OR . . DISTRIBUTION...... 2 Virus File 1-1: Use of PubMed, ScienceDirect, CDC Publications, ProMED-mail, and HealthMap to Research Specific Viruses or to Monitor Viral Outbreaks...... 19 Virus File 1-2: “Now I Take My Pen in Hand …”: Letters by a Wisconsin Soldier During the Civil War ©Chronicle Jones Disease & Bartlett. . . .Learning, ...... LLC ...... ©. .Jones . . & Bartlett 35Learning, LLC Case Study 2: TickborneNOT Heartland FOR Virus SALE. . . OR. . .DISTRIBUTION ...... NOT . . . FOR SALE OR62 DISTRIBUTION

Chapter 2 Case Study 1: A Lurking in Contact Lens Solution...... 73 Virus ©File Jones 2-1: Disco & veryBartlett of a Big Learning, and Bizarre LLC Virus...... © . .Jones . . . . .& . Bartlett. . . . Learning, LLC83 Virus NOTFile 2-2 FOR: The Race SALE to CharacterizeOR DISTRIBUTION SARS-CoV...... NOT . . . . .FOR . . . SALE OR DISTRIBUTION88 Case Study 2: Mysterious Bald Eagle Die-Offs ...... 96

Chapter 3 © Jones Case& Bartlett Study 1: The Learning, Motives of LLC Ebola Virus...... © . Jones . . . . .& . Bartlett . . . . . Learning,...... LLC. 101 NOT FORVirus SALE File 3-1 OR: RNA DISTRIBUTION Splicing: A Teachable Moment by AdenovirusNOT FOR 2. . SALE. . . . . OR. . . DISTRIBUTION...... 109

viii Contents © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 8 04/07/16 9:11 am Virus File 3-2: How Are Cellular Receptors Used for Viral Attachment Discovered?...... 126 © Jones & Bartlett Learning, LLC © Jones &Virus Bartlett File 3-3 Learning,: Unraveling theLLC Replication Cycle of ...... 132 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Refresher: Molecular Biology...... 134 Virus File 3-4: Real-Time Virus Tracking in Live Cells...... 138 Virus File 3-5: Discovery Through Reverse Pharmacology ...... 147 Case Study 2: A Rabies© VirusJones with & an Bartlett Abortive Learning, Replication Cycle?LLC ...... © . .Jones . . . . & . . Bartlett Learning,149 LLC Case Study 3: MysteriousNOT Rashes FOR .SALE . . . . .OR . . .DISTRIBUTION ...... NOT. FOR SALE OR151 DISTRIBUTION Case Study 4: at a Day Care Facility...... 151

Chapter 4 Case© Study Jones 1: The & WorriesBartlett of TurkeyLearning, Farmers LLC...... © . .Jones . . . . &. .Bartlett . . . . . Learning, . LLC157 VirusNOT File 4-1 FOR: Rabies SALE Transmission: OR DISTRIBUTION Human Rabies Caused by Tiny BatNOT Bites .FOR . . . SALE. . . . .OR . . DISTRIBUTION. . . . 164 Virus File 4-2: Isolated Reminders of 19th-Century Smallpox Epidemics in America...... 171 Virus File 4-3: Is Groundwater Safe to Drink?...... 186 Case Study 2: Disturbing Cow Patties...... 190 © Jones &Case Bartlett Study 3 Learning,: Screening Travelers LLC for SARS-CoV Infection© Jones at Airports & Bartlett...... Learning, ...... LLC . . . . . 193 NOT FOR CaseSALE Study OR 4: ADISTRIBUTION Multidrug-Resistant Strain of HIV . . .NOT . . . FOR. . . .SALE . . . . OR . . .DISTRIBUTION ...... 194 Case Study 5: A Reemerging Adenovirus That Causes Severe Illness...... 196 Case Study 6: The Rabid Batman Tragedy ...... 196 Case Study 7: A Smallpox Biohazard?...... 197 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONChapter 5 NOT FOR SALE OR DISTRIBUTION Case Study 1: Surviving Ebola Virus Disease...... 203 Virus File 5-1: The Massie Puzzle Piece Hiding on Chromosome 6...... 210 Refresher: Immunology ...... 215 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Virus File 5-2: Wakefield’s Syndrome (“Autistic Enterocolitis”) and the MMR Vaccination Scare...... 246 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Case Study 2: Lymphocytic Choriomeningitis Virus: A Virus from Cute Pet Rodents...... 258 Case Study 3: in College...... 259

Chapter 6 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Case Study 1: Virus Cold Cases: Brainerd Diarrhea, Sweating Sickness, and Picardy Sweat ...... 265 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Virus File 6-1: Impact of Viruses on War and Religion...... 277 Virus File 6-2: Descriptive Epidemiology and AIDS...... 282 Virus File 6-3: Sentinel Chicken Surveillance Programs ...... 288 Virus File 6-4: Today’s© Virus Jones Hunters: & Bartlett C . J . Peters Learning, and W . Ian LLC Lipkin...... © . Jones . . . . .& . Bartlett Learning,289 LLC Virus File 6-5: VoluntaryNOT Quarantine FOR SALE and the OR Village DISTRIBUTION of Eyam ...... NOT . . . FOR. . . . SALE OR292 DISTRIBUTION Case Study 2: Viral Linked to Swimming Pool...... 314 Case Study 3: Musicians and Viral Infections...... 315 Case Study 4: Yellow Fever Virus During a Vacation to Brazil...... 315 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Chapter 7 NOT FOR SALE OR DISTRIBUTION Case Study 1: Cluster of and Encephalitis Cases...... 321 Refresher: PCR...... 324 Refresher: Immunology Terms ...... 331 © Jones &Virus Bartlett File 7-1 Learning,: Diagnosis of LLC Severe Acute Respiratory ©Syndrome Jones (SARS)& Bartlett and Middle Learning, East Respiratory LLC NOT FOR SALE OR DISTRIBUTIONSyndrome (MERS) Caused by Novel CoronavirusesNOT FOR. . SALE ...... OR . . . DISTRIBUTION...... 338

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9781284057898_FMxx_00i_xxiv.indd 9 04/07/16 9:11 am © JonesVirus & Bartlett File 7-2: DevelopmentLearning, LLCof a Rapid Test to Determine© WhetherJones &Respiratory Bartlett Illnesses Learning, Are LLC NOT FOR SALE ORCaused DISTRIBUTION by a Virus or Bacterium...... NOT . . . FOR. . . .SALE . . . . OR . . .DISTRIBUTION ...... 342 Refresher: Restriction ...... 354 Case Study 2: Severe Brain Infections in Africa and Vietnam Associated with a New Mysterious . . . . 357

© Jones & Bartlett Learning,Chapter LLC 8 © Jones & Bartlett Learning, LLC Case Study 1: PoliomyelitisNOT and FOR Measles SALE in the OR Amish DISTRIBUTION Community...... NOT. . . . FOR . . . SALE OR362 DISTRIBUTION ViruS File 8-1: Creating Poliovirus in a Test Tube...... 3 74 ViruS File 8-2: Using Google Earth to Track Poliovirus down the Congo River...... 382 Case Study 2: Echovirus 4...... 388 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Chapter 9 NOT FOR SALE OR DISTRIBUTION Case Study 1: Commingling of , Pigs, and Variant Influenza Viruses at U .S . County Fairs...... 393 Virus File 9-1: Retrospective Study Examining the Impact of the 1918 Influenza Pandemic on a Wisconsin Community...... 395 © Jones Virus& Bartlett File 9-2: TheLearning, Perfect Storm LLC of Cytokines That Can Kill© Jones You. . . &. .Bartlett . . . . . Learning, ...... LLC . . . . 404 NOT FORVirus SALE File 9-3 OR: Using DISTRIBUTION -Based Reverse Genetics toNOT Produce FOR Avian SALE Influenza OR DISTRIBUTION A (H5N1) Vaccines...... 426 Case Study 2: Human ...... 445 Case Study 3: Influenza Diagnostics...... 446 Case Study 4: Seasonal InfluenzaVaccines ...... 447 Case Study 5: Avian Influenza© Jones on & U .S Bartlett. Poultry Farms Learning,. . . . . LLC ...... © . Jones. . . . & Bartlett447 Learning, LLC Case Study 6: Sick DogsNOT and CatsFOR. . .SALE . . . . OR. . . DISTRIBUTION...... NOT FOR SALE OR448 DISTRIBUTION

Chapter 10 Case Study 1: Contaminated Oranges for Tourists in Egypt...... 454 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Virus File 10-1: Human Viruses Lurking in Porta-Potties and Outhouses...... 456 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Virus File 10-2: A Breakthrough for Virus Research...... 482 Case Study 2: Killer Salsa...... 487 Case Study 3: Bob Massie and Bloodborne Infections ...... 487 Case Study 4: Flooding with Viruses...... 488 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 11 Case Study 1: Chickenpox Lollipops...... 492 Virus File 11-1: Are Oyster Herpes Outbreaks a Symptom of Global Climate Change?...... 493 Virus File 11-2: Does Epstein-B© Jonesarr Virus& Bartlett Play a Role Learning, in the Development LLC of Multiple Sclerosis?© Jones. . . . & . Bartlett. . . 500 Learning, LLC Case Study 2: Why Is It NOTCalled FOR “Chickenpox”? SALE OR. . DISTRIBUTION...... NOT. . . . FOR SALE OR520 DISTRIBUTION Case Study 3: Wrestlers with “Mat Herpes”...... 521 Case Study 4: Elephant Herpes...... 522 Case Study 5: Are HSV-1 and CMV Related to the “Stupidity Virus”?...... 522 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Chapter 12 NOT FOR SALE OR DISTRIBUTION Case Study 1: 2015 HIV Outbreak in a Small Town in Indiana: A Warning to Rural America ...... 528 Virus File 12-1: Transmission of HIV by Dental Procedure...... 539 Virus File 12-2: Shutting the Cellular Door to HIV-1: Research Toward a Cure...... 572 © Jones Case& Bartlett Study 2: MagicLearning, Johnson LLC and HIV ...... © . Jones. . . . . & . Bartlett...... Learning, ...... LLC 578 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

x Contents © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 10 04/07/16 9:11 am © Jones & Bartlett Learning, LLC Chapter© Jones 13 & Bartlett Learning, LLC NOT FOR CaseSALE Study OR 1: Poe’sDISTRIBUTION Mysterious Death ...... NOT . . . FOR. . . .SALE . . . . OR . . .DISTRIBUTION ...... 585 Refresher: What Is Encephalitis? ...... 595 Virus File 13-1: Why Did Jeanna Giese Survive?...... 599 Case Study 2: A Rabid Cow Named Millie...... 611 Case Study 3: Texas Teen© Jones Rabies &Case Bartlett...... Learning, ...... LLC ...... © Jones & Bartlett Learning,611 LLC Case Study 4: Rabid DogsNOT in FOR China SALE. . . . .OR . . DISTRIBUTION...... NOT . . . . FOR SALE OR612 DISTRIBUTION

Chapter 14 Case Study 1: Squirrelpox ...... 617 Virus© File Jones 14-1: Deliberate& Bartlett Use Learning, of Myxoma LLC Poxviruses to Control Australian© Jones Wild Rabbits& Bartlett...... Learning, . . . . . LLC631 VirusNOT File 14-2 FOR: Farmer SALE Jesty OR and DISTRIBUTION the Importance of Self-Promotion. .NOT . . . .FOR . . . SALE . . . . OR. . .DISTRIBUTION . . . 633 Case Study 2: Smallpox Vaccination...... 643 Case Study 3: An Envelope of Smallpox Scabs...... 644 Case Study 4: Laboratory-Acquired Cowpox...... 645 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 15 Case Study 1: Post-Ebola Syndrome? ...... 650 Virus File 15-1: Brain-Shrinking Zika Virus Bound for the United States? ...... 662 Virus File 15-2: Retrovir© usesJones Crossing & Bartlett the Species Learning, Barrier inLLC Nature: Hunters in Africa Infected© Jones with & Bartlett Learning, LLC Retroviruses Through Bushmeat...... 668 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Virus File 15-3: Human Bocavirus (HBoV): An Emerging Viral ?...... 676 Case Study 2: Sick Horses...... 681 Case Study 3: Borna Disease...... 681 Case© Study Jones 4: My &sterious Bartlett Pig Learning, Mortalities. LLC...... © . .Jones . . . . & . .Bartlett . . . . . Learning, LLC682 CaseNOT Study FOR 5: Puzzling SALE Illness OR AmongDISTRIBUTION Colorado Field Workers...... NOT . . . FOR . . . .SALE . . . . OR . . .DISTRIBUTION . 682 Case Study 6: Baffling Respiratory Distress in Pigs...... 683

Chapter 16 © Jones &Case Bartlett Study 1 Learning,: Dr . Dock’s 1896–1897 LLC Observations of Cancer© Jones Remission & Bartlett After “BoutLearning, with Influenza” LLC . . . . . 687 NOT FOR VirusSALE File OR 16-1 :DISTRIBUTION Cell Cycle and Cancer Biology DefinitionsNOT. . FOR. . . .SALE . . . . OR . . .DISTRIBUTION ...... 692 Virus File 16-2: Alien DNA and Schizophrenia...... 701 Virus File 16-3: The Pap Test Controversy: Papanicolaou vs . Babes...... 707 Virus File 16-4: Covered in Warts, “Tree Man” Dies of Rare Disease...... 710 Virus File 16-5: Mouth© and Jones Throat & Cancer Bartlett and Learning,Oral Sex . . .LLC ...... © . Jones . . . . . & Bartlett Learning,714 LLC Virus File 16-6: The SVNOT-40 Controversy: FOR SALE Passenger OR DISTRIBUTION or Emerging Pathogen? Will SV-40 LargeNOT T FOR SALE OR DISTRIBUTION Vaccination Become Routine?...... 719 Case Study 2: Mysterious Hepatitis Symptoms...... 737 Case Study 3: Virotherapy in the Movies...... 738 Case© Study Jones 4: Inf &ectobesity Bartlett. .Learning, ...... LLC ...... © . Jones...... & . Bartlett . Learning, LLC738 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 17 Case Study 1: Can a Shot of Poliovirus Cure Cancer?...... 74 5 Virus File 17-1: Eight Years HIV-Free: Timothy Ray Brown Cured...... 74 8 © Jones &Virus Bartlett File 17-2 Learning,: Rabies Transmission LLC from Solid-Organ ©Transplants Jones &. . .Bartlett ...... Learning, ...... LLC . . . 763 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Contents xi © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 11 04/07/16 9:11 am © JonesCase & Bartlett Study 2: Xenozoonosis Learning, LLC...... ©. .Jones . . . . &. .Bartlett . . . . . Learning, ...... LLC 768 NOT FORCase SALE Study OR3: Gene DISTRIBUTION Therapy ...... NOT. . . .FOR . . . SALE . . . . OR. . . DISTRIBUTION . . . . . 768 Case Study 4: Using Gene Therapy to Treat Cancer...... 769

Chapter 18 Case Study 1: Mysterious© JonesIllness in & a BartlettCat Owner Learning,...... LLC ...... © . Jones. . . & Bartlett772 Learning, LLC Virus File 18-1: Point–Counterpoint:NOT FOR SALEIs Spiroplasma OR DISTRIBUTION Involved in TSEs? The Scientific DebateNOT. . . . FOR . . . . .SALE . OR788 DISTRIBUTION Case Study 2: CJD-Like Illness Among Consumers of Squirrel Brains ...... 793 Case Study 3: CJD-Like Illness Among Deer Hunters...... 794 Case Study 4: Human-to-Human CJD Transmission ...... 794 Case Study© Jones 5: Decont & Bartlettaminated Learning,Surgical Instruments LLC ...... ©. .Jones . . . . &. .Bartlett . . . . . Learning, . LLC795 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 19 Case Study 1: Plum Pox...... 799 Virus File 19-1: Silencing Genes ...... 810 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chapter 20 Case Study 1: Phage Therapy Resuscitated...... 827 Virus File 20-1: Bacteriophage Therapy Makes a Comeback...... 830 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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Despite progress over the past century, the world animals are seen as one “contiguous population,” continues to face substantial,© Jones and & evenBartlett growing, Learning, is critical. LLC © Jones & Bartlett Learning, LLC infectious disease challenges,NOT FOR including SALE OR DISTRIBUTION The threat of new pandemicsNOT fosters FOR inno SALE- OR DISTRIBUTION resistance; Ebola; Zika; Middle East respiratory vation and opportunities for collaboration and syndrome (MERS); avian influenza, including sharing, among countries and across govern- H5N1 and H7N9; , and even HIV/ ments. Global health is driving interdisciplinary AIDS. These diseases present challenges that are in approaches in education, requiring students to need© of Jonestechnological & Bartlett advancements Learning, (e.g., LLC devel- synthesize, evaluate,© Jones and &apply Bartlett knowledge Learning, rel- LLC opmentNOT of FORrapid diagnosticsSALE OR and DISTRIBUTION new drugs and evant to complexNOT real-world FOR SALE challenges, OR DISTRIBUTIONsuch as vaccines) and the political commitment to invest emerging viruses that are contributors to the rise in global prevention and control. The subsequent of infectious disease outbreaks. Embracing global reviews of the public health response to the Ebola health through undergraduate liberal arts pro- outbreak in West Africa by three different groups grams in education makes it possible for students © Jones &exposed Bartlett the Learning, major gaps LLC in our public health ©to Jones connect & classroom Bartlett learning Learning, to field LLC testing of NOT FORand SALE medical OR capability DISTRIBUTION to rapidly and effectively NOTsolutions. FOR Students SALE whoOR DISTRIBUTIONare encouraged to think address these ever-increasing infectious disease creatively and holistically about global health crises. challenges may foster a culture of reciprocity. A number of factors favor the emergence of infectious diseases in our 21st-century world. International travel© andJones commerce & Bartlett greatly Learning, LLC © Jones & Bartlett Learning, LLC enhance the movementNOT of FOR infected SALE people OR and DISTRIBUTION NOT FOR SALE OR DISTRIBUTION animals, including arthropod vectors, throughout the world. Rapid growth in both human and food- production animal populations creates the ideal environment for mixing and the emergence of new infectious© Jones disease & problemsBartlett and Learning, the reemergence LLC © Jones & Bartlett Learning, LLC of previousNOT FOR infectious SALE challenges. OR DISTRIBUTION Today, with a NOT FOR SALE OR DISTRIBUTION global human population of 7.4 billion people, one out of every eight people who has ever lived is currently on the face of the earth. Population growth is greatest in developing world megacities, © Jones &where Bartlett the squalid Learning, conditions LLC of slums, with mil- © Jones & Bartlett Learning, LLC NOT FORlions SALE of people, OR DISTRIBUTION greatly enhances the likelihood of NOT FOR SALE OR DISTRIBUTION the rapid emergence of infectious diseases. © Bloomberg/Getty Images. Although it may be impossible to predict Michael t . Osterholm, PhD, MPH which may emerge or reemerge into Regents Professor a potential global crisis, early detection through McKnight Endowed Presidential Chair in Public Health comprehensive disease© Jonessurveillance & Bartlett systems Learning,is a Director, LLC Center for Infectious Disease© Research Jones and & Policy Bartlett Learning, LLC key factor in respondingNOT to FORthese SALEepidemics. OR We DISTRIBUTION Distinguished University Teaching ProfessorNOT FOR SALE OR DISTRIBUTION must also keep focused on the transmission of Environmental Health Sciences, School of Public Health infectious diseases at the human–animal inter- Professor, Technological Leadership Institute College of face, because so many current diseases are zoo- Science and Engineering noses, diseases transmitted between humans and Adjunct Professor, Medical School animals.© Jones This is & why Bartlett a “one Learning,health approach” LLC to http://www .cidrap© .umn Jones .edu & Bartlett Learning, LLC reducingNOT infectious FOR SALE diseases, OR where DISTRIBUTION humans and NOT FOR SALE OR DISTRIBUTION

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9781284057898_FMxx_00i_xxiv.indd 13 04/07/16 9:11 am © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE ORP DISTRIBUTIONreface NOT FOR SALE OR DISTRIBUTION

This third edition of Understanding Viruses is the prod- uct of nearly© 20 Jones years of & teaching Bartlett introductory Learning, virol LLC- New to This© E Jonesdition & Bartlett Learning, LLC ogy to undergraduateNOT FOR students SALE majoring OR DISTRIBUTION in biology, NOT FOR SALE OR DISTRIBUTION microbiology, and medical technology and to premed Understanding Viruses, Third Edition contains a and other preprofessional students. Because many of Foreword by Dr. Michael T. Osterholm that dis- the students in my courses had not taken a micro- cusses the fast-paced and interdisciplinary nature biology or cellular and molecular biology course, I of . The revision was focused on address- © Jonesfound &that Bartlett they lacked Learning, knowledge LLC about the fun- ing peer© Jones reviews, & improving Bartlett the Learning, text’s content LLC and NOTdamental FOR SALE concepts OR of DISTRIBUTIONcell biology and needed some overallNOT quality. FOR For SALE this reason, OR DISTRIBUTIONthe order of chap- form of “refresher” to aid them through the course ters has been rearranged slightly to accommodate material. It was a struggle to find a textbook that reviewers’ comments. For example, “Viruses and combined a holistic approach to understanding viral Cancer” has been moved to Chapter 16, and “The diseases. Most virology textbooks are focused on the History of Medicine, Clinical Trials, Gene Ther- © Jones & Bartlettpathogenesis/clinical Learning, LLC aspect of viral diseases or© theJones apy,& Bartlett and Xenotransplantation” Learning, LLC has been moved NOT FOR SALE ORmolecular DISTRIBUTION biology of viral replication. StudentsNOT were FORto SALE Chapter OR 17, DISTRIBUTIONbecause this information may not more enthusiastic to learn the molecular aspects of be covered in a one-semester course. Although it viral diseases if the historical and clinical perspec- is impossible to create a textbook that is current tives were presented with it. Understanding Viruses, with most recent events and discoveries, every Third Edition uses an interdisciplinary approach by effort has been made to include the most up-to- covering the© historical Jones &perspectives Bartlett alongLearning, with the LLC date information before© Jonesthe text &was Bartlett printed. Learning,For LLC molecular biologyNOT FORof virus SALE structure OR and DISTRIBUTION replication, example, it includes NOTnew information FOR SALE about OR the DISTRIBUTION pathobiology (the observed nature of disease, its Ebola epidemic in West Africa and information on causes, processes, development, and consequences), the Zika virus epidemic in Brazil that was taking and epidemiological impact of viral diseases on local place while the text was in production. and global populations. All chapters in this edition now open with a © JonesVirology & Bartlett is a dynamic Learning, discipline. LLC Emerging quote,© relevant Jones opener & Bartlett figure, Learning, case study, andLLC a set NOTviral FOR diseases SALE such OR asDISTRIBUTION the 2014–2015 Ebola epi- of learningNOT FORobjectives. SALE Much OR effort DISTRIBUTION has been put demic in West Africa; the spread of Zika virus into restructuring and updating the introductory infections to Brazil in 2015, which was associated chapters of the textbook. Chapter 1 includes sev- with microcephaly in newborns; the threat of eral new topics, including how scientists can learn pandemic avian influenza A viruses; the spread from viruses, helpful or collaborative viruses, © Jones & Bartlettof ChikungunyaLearning, LLC virus infections to the Americas© Jones human& Bartlett and aquaticLearning, viromes, LLC and a brief intro- NOT FOR SALE ORin 2013; DISTRIBUTION the impact of global climate changeNOT on FORduction SALE to OR epidemiology DISTRIBUTION through coverage of the infectious disease (e.g. insect vectors); the need for transmission and pathogenesis of viral infections. the development of new vaccines and antivirals Chapter 1 summarizes recent epidemics caused by to combat viral diseases; and new cancer thera- Ebola virus in West Africa, hantavirus in Yosemite pies that utilize viruses to replicate within cancer National Park, Middle East respiratory syndrome, cells and kill© Jonesthem while & Bartlett inducing Learning, the adaptive LLC measles virus in the United© Jones States, & Bartlettand Schmal Learning,- LLC immunity ofNOT the body FOR to SALEattack and OR destroy DISTRIBUTION tumor lenberg viruses in Europe.NOT FOR SALE OR DISTRIBUTION cells are popular topics covered by news media. My Chapters 2 and 4 have been merged to create intent was to create a resource that provides a “big Chapter 3. This chapter now presents an overview picture” or systematic approach to understand- of eucaryotic molecular biology, along with the ing viruses, including historical perspectives and basics of virus replication, as a refresher for those © Jonesepidemiological & Bartlett accounts Learning, of viral LLC diseases, along students© Jones lacking & prerequisite Bartlett Learning, knowledge LLC of cell NOTwith FOR the SALE relationships OR DISTRIBUTION between the host, virus, biology.NOT It containsFOR SALE new ORVirus DISTRIBUTION File boxes about and environment (disease triangle model of dis- RNA splicing (reviewing early experiments on ade- ease causation) and the molecular biology of viral novirus R-loop mapping), real-time virus tracking structure and replication. in live cells, and a reverse pharmacology approach © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

xiv © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 14 04/07/16 9:11 am to antiviral drug discovery. It also explores the molecular in other resources are bundled with the textbook. The © Jones hurdles& Bartlett overcome Learning, by replicating LLC viruses through inclu©- Jonesanimations & Bartlett in Understanding Learning, Viruses LLC are used to explain NOT FORsion SALE of such OR topics DISTRIBUTION as host cell receptors and polymerases,NOT FORthe mechanisms SALE OR of DISTRIBUTION the following antivirals: actin remodeling, and viral mRNA compatibil- ity, and the competition between virus–host cell mRNAs •• Neuraminidase inhibitors of influenza A viruses for cellular translational machinery. •• HIV protease inhibitors A concerted effort has been made to provide examples •• HIV integrase inhibitors of worldwide epidemics© Jonescaused by & viruses. Bartlett The Learning, majority LLC•• Herpesvirus acyclovir© inhibitorJones & Bartlett Learning, LLC of the chapters containNOT new FOR chapter SALE opener OR figures DISTRIBUTION and •• proteaseNOT inhibitorsFOR SALE OR DISTRIBUTION introductory case studies. There are new case studies •• ZMapp inhibitor of Ebola virus about Ebola, West Nile, variola, varicella zoster, measles, avian and swine influenza A, Heartland and amoebic To ensure that students become familiar with credible viruses; human immunodeficiency virus (HIV, in partic- resources beyond the classroom, numerous tables and ular the© Jones2015 epidemic & Bartlett in Indiana); Learning, and other LLC topics, such maps are ©provided Jones that & presentBartlett epidemiological Learning, LLCinforma- as theNOT use of FOR a modified SALE poliovirusOR DISTRIBUTION to treat glioblastoma. tion. ChapterNOT 6 FORcontains SALE tables OR that DISTRIBUTION list modes of trans- Case studies include a list of references that were used to mission, incubation periods, and R-nought values for create the case study and questions to involve students various viral diseases, as well as website addresses for in problem-solving activities, higher-order thinking, and traveler’s health information and global partnerships. opportunities to extend their learning. Additional chapters contain lists of FDA-approved anti- © Jones & BartlettAlong with Learning, the global LLCapproach to viral diseases, we© Jonesviral & drugs, Bartlett vaccination Learning, recommendation LLC schedules, and NOT FORhave SALE incorporated OR DISTRIBUTION terminology associated with viral disNOT- FORlists of SALE vaccines OR in useDISTRIBUTION today. eases used by the World Health Organization (WHO) and For the first time, this new edition includes appen- the Centers for Disease Control and Prevention (CDC). dices containing in-depth information on a number of New Virus Files are provided throughout the textbook topics that may be of interest to students: on a variety of engaging topics: © Jones & Bartlett Learning, LLC•• Appendix A: Properties© Jones of Human & BartlettViruses Learning, LLC •• “Now I take MyNOT Pen inFOR Hand SALE . . .” (letters OR DISTRIBUTION from a •• Appendix B: BaltimoreNOT Virus FOR Classification SALE OR DISTRIBUTION Wisconsin soldier chronicling disease during the •• Appendix C: Bonus case study: “Combating the Civil War) Worst Epidemic of Ebola Virus Disease in Human •• Isolated Reminders of Smallpox Epidemics During History” the 1800s in America •• ©Wakefield’s Jones & BartlettSyndrome Learning, (“Autistic Enterocolitis”)LLC This text© is Jonesunlike many & Bartlett others Learning,on the market LLC today. NOTand the FOR MMR SALE Vaccination OR DISTRIBUTION Scare The end ofNOT every FOR chapter SALE contains OR additionalDISTRIBUTION cases stud- •• The Massie Puzzle Piece Hiding on Chromosome 6 ies with questions and a list of resources that have been •• Virus Cold Cases: Brainerd Diarrhea, Sweating updated and separated into primary literature, reviews, Sickness, and Picardy Sweat popular press books, and video productions (listed in •• Development of a Rapid Test to Determine if Respi- reverse chronological order). These resources allow © Jones & Bartlettratory Illnesses Learning, Are Caused LLC by a Virus or Bacterium© Jonesfor flexibility& Bartlett in Learning,course design. LLC Primary literature and NOT FOR SALE•• Human OR DISTRIBUTIONViruses Lurking in Porta-Potties andNOT FORreviews SALE can be OR assigned DISTRIBUTION as outside readings to engage Outhouses and familiarize students during class discussions and to •• Voluntary Quarantine and the Village of Eyam inform debates about discoveries and current topics in •• The Pap-Test Controversy: Papanicolaou vs. Babes the field of virology. Video resources serve as excellent •• Brain-Shrinking Zika Virus Bound for the United and timely supplements to the text. The glossary was States? © Jones & Bartlett Learning, LLCrevised extensively. The textbook© Jones is not & theBartlett only tool Learning, for LLC NOT FOR SALE OR DISTRIBUTIONinstruction, but rather a NOTguide thatFOR can SALE be judiciously OR DISTRIBUTION The book includes a consistent art package of illustra- adapted to a graduate-level virology course. tions. For the first time, animations previously not found

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Preface xv © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 15 04/07/16 9:11 am ChaPter 8 © JonesThe & Bartlett Student Learning, Experience LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The main goals in the development of the third edition of biology students are expected to include, such as e-book Development of a Rapid Test to Determine Whether Respiratory illnesses Undertanding Viruses have been to arouse student interest access and other current pedagogy that engages students ViRus filE 7-2 Are Caused by a Virus or Bacterium and to create a tool for instruction that contains Poliovirus all of the andin the Otherlearning process. Enteroviruses The textbook has a number of spe- educational “bells and whistles” that books for first-year cial features to prompt student engagement and interest: All too often a person shows up at a clinic or hospital emergency room suffering from symptoms of a © Jones & Bartlett Learning,“ The fight against LLC © Jones & Bartlett Learning, LLC respiratory tract infection and the doctor prescribes just in case the patient is suffering from infantile paralysis is a a bacterial infection. Antibiotics will not work if a virus is the cause of the illness. Symptoms alone are NOT FOR SALE ORfight to DISTRIBUTIONthe finish, and the NOT FOR SALE OR DISTRIBUTION not enough to diagnose a respiratory infection. Today, if it is influenza season a rapid test may be done to . terms are unconditionalsurrender ” determine whether the patient is suffering from influenza A or B or strep throat caused by the bacterium Streptococcus pyogenes. A group of researchers at Duke University are developing a rapid blood test that can distinguish whether —Franklin Delano Roosevelt, 32nd U.S. president and a respiratory illness is caused by a viral or bacterial pathogen. In order to develop the test, small studies polio survivor (1944) were done using healthy volunteers who). The agreed Duke to be infected with different strains of . Learning Objectives iguRE 1 Draped overDescribe the handlebars the ofproperties a of enteroviruses that contribute to their stability in the environment. Their blood was drawn during the course of infec- bicycle1. in the Central African tion and genetically analyzed (f © Jones & Bartlett Learning, LLC country2. Explain of Chad isthe a satchel role of proteases in the© poliovirus Jones replication & cycle. Bartlett Learning, LLC containing poliovirus vaccine. The researchers discovered that the expression of 30 satchel3. includesEvaluate a logo the with rationale the by CDC experts to remove the Sabin vaccine from the vaccination cellular genes involved in the NOT FOR SALE OR DISTRIBUTION recommendations to prevent poliomyelitisNOT in FOR the United SALE States. OR DISTRIBUTION words “Kick Polio out of Africa.” The were turned on in different ways during the viral Learning Objectives—NEW to the third bicycle is used as transportation to deliver poliovirus4. Define vaccine post-polio to out-of- syndrome, and identify who is particularly vulnerable to it. infection. The cellular immune response was the-way villages that are far from edition, these give students a concise Discuss why poliovirus eradiation remains unfinished business. referred to as a specific viral or genetic signature. more urbanized5. areas of the country. When infected by a virus, a person’s immune overview of the important chapter The global 6.effort List to eradicate the signs polio andis symptoms of infectious diseases caused by nonpolio enteroviruses. the largest public health initiative in system responds differently than it would when

human history.Note It began the in importance 1988 by H. M.P. Kurnit, CDC/Molly the of ofCourtesy emerging enteroviruses, such as D68. 7. fighting a bacterial infection. The researchers concepts they will be asked to master. the WHO with the goal of eradicating polio by the yearnot 2000. been This met goal to date.has developed an RT-PCR test to detect the viral © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,Poliovirus LLC Eradication is unfi nished 8.10 signature of influenza A viruses in patient blood O U t L i n e Business samples. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTIONOther Enteroviruses (Nonpolio Viruses) The viral signatures of the volunteers infected Case study 1: Poliomyelitis 8.11 and measles in Chapter Outlines—A detailed outline at Brief Overview of Enteroviruses and Dilated Cardiomyopathy with influenza A viruses were compared to blood 8.1 the amish Community Langerhan’s cells); mucous membranes; and the lin- the beginning of the chapter offers a The History of Polio Respiratory Enteroviruses: samples collected from people whoing wentof the to nose, lungs, and gastrointestinal tract. Medi- 8.2 Triggering Asthma Clinical Features of Poliomyelitis hospital emergency rooms complainingcal graduate of fever student Paul Langerhan, who was working 8.3 quick snapshot of the topics that will be Enteroviruses 71 and D68: Reemerging and respiratory illness. Their rapidunder blood thetest mentorship of Professor Rudolf Virchow at Post-Poliomyelitis Syndrome α defensins have been shown to block infection Viral Pathogens? The identified positive viral signaturesthe or Instituteinfections of in of the University of Berlin in presented. In July 2005,Classifi a 7-month-oldcation and Structure unvaccinated of Poliovirus Amish 8.4 of different naked viruses by such89% mechanisms of the cases as and the correctly ruled1868, out first nega- described Langerhan’s cells. In his 1868 land- infant girl was hospitalized in a central Minnesota hos- Summary Stability of Enteroviruses in the Environment aggregation or clumping of naked tiveviruses cases on 94% the surfaceof the time. Earlymark differentiation paper, “Uber die Nerven der menslichen Haut,” © Jones & Bartlett Learning,pital because LLCshe was failing to thrive. The child suf- resources© Jones & Bartlett Learning, LLC laboratory Diagnosis of Poliovirus of host cells (e.g., BK viruses are inhibited this way), the Langerhan described the cells as nerve endings ofCourtesy the of Amanda Mills/CDC. fered 8.5 from diarrhea and recurrent infections. She was Poliomyelitis and Measles in the between viral and bacterial- respiratory infec- infections Case Study 1: inhibition of viral uncoating (e.g., human adenoviruses), skin. In 1882 he corrected his interpretation, stating, “I NOT FOR SALE OR DISTRIBUTIONplaced in isolation and evaluated for a bone marrow NOT FOR SALE OR DISTRIBUTION tions can direct treatment appropriately (e.g., - transplant Cellularafter the Pathogenesis results of medical laboratory tests Amish Community and by blocking the viral from entering the am now convinced that my cells are in no way essential). Den Echovirus 4 Tamiflu for influenza A patients who are at high Test tube rack containing purple-capped- blood indicated 8.6 she was severely immunocompromised. iguRE 1 Case Studies—Real-world cases are presented Poliovirus replication Case Study 2: nucleus of its host cell (e.g., humanrisk papillomaviruses). for complications of influenzafor Anerve infection). endings.” f Refresher: Immunology 8.7Meanwhile, experts at the Minnesota Department Creating Poliovirus in a Test Tube β defensins block enveloped viruses such as respira MHC class I andcollection II molecules tubes. In are the expressed future, blood on may the be analyzed for ViruS FilE 8-1: The of Health Treatments(MDH) isolated an enterovirus from the Using Google Earth to Track Poliovirus It can curb the misuse of antibiotics or improve profiles of immune system genes 5-6 expressed). during at the beginning of each chapter and connected 8.8 © Teri Shors. tory syncytial virus and human parainfluenza virus type surfaces of dendritic cells (see FiguRE ViruS FilE 8-2: triage in settings of a potential pandemic. The infection for diagnostic purposes. girl’s stool Preventionsample. The enterovirus was identified as a 3 from viral entry into host cells by interacting directly dritic cells act as scouts that are very efficient at identify vaccine-derived 8.9 poliovirus. The genomic sequence of down the Congo River development of this rapid diagnostic assay and with questions placed at the end of the chapter Chemicals and Gamma Globulin with them. The defensins disrupt defensins the viral inhibit envelope, herpes ing foreign invaders such as viruses and bacteria, even the enterovirus, however, was determined to be 2.3% and β inactivating the virus’s infectivityits (i.e., testing ability in a “real-world”to enter patientwhen setting they are are present in minute numbers ( cells are in order to promote student interest and engage- different from Inactivated the parent Vaccines Sabin poliovirus type 1 strain, Amish do not object to vaccination, but significant H Figure 1 into host cells). Both α paving the way for establishing thisDendritic new type cells of internalize the pathogen,H cells. digest (T it, and © Jones & Bartlett Learning, LLC and it was Theestimated Cutter Incident that it was© replicatingJones for about & Bartlettpockets of lower Learning, vaccination rates may exist inLLC Amish communities. 361 ment. Additional Case Studies at the end of most 2 years in an immunocompromised individual. Oral simplex virus (an enveloped virus)diagnostic by blocking testing in thethe clinic. display or present the foreign peptides on their surface Live, Attenuated Poliovirus Vaccines poliovirus vaccine (OPV) is still widely used in most cellular receptor present on the surface of its host cell, using the MHC II molecules to T chaptersNOT provide FOR additional SALE real-worldOR DISTRIBUTION examples NOT FOR SALE OR DISTRIBUTION References Learning Objectives countries, but it has not been used in the United States contracted measles while on a mission trip to the Phil- preventing entry into the host cell.Ramilo, O., et al. 2007. “Gene expression describedpatterns in blood later leukocytes in this discriminate chapter patterns as part with of acute the infections.” discussion Blood 109:2066–2077. ). Amish or Hutterite 30/05/16 10:47 am since 2000 and in Canada sinceFigure 1997. 1 ippines. The men returned to the United States and Zaas, A. K., et al. 2013. “A host-based RT-PCRon specific gene expression immune signature defenses.) to identify Activatedacute respiratory dendritic viral infection.” cells Sci Transl Med and applications1. Describe the of properties the of chapter enteroviruses that content. contribute to their stability in the environment. Old Order Amish and Amish Mennonite views about 5:203ra126. thought they had dengue fever, which is not conta- Dendritic cells also express high levels of another surface receptor, B7, 2. Explain the role of proteases in the poliovirus replication cycle. vaccination vary widely ( gious. They attended church to pray for a fast recovery. dendritic cells are covered with long, spiky arms that 3. Evaluate the rationale by CDC experts to remove the Sabin vaccine from the vaccination religious doctrine does not prohibit vaccination, but Instead, Amish at the church were exposed to the, of mea 18. -In 0 resemble the dendrites of nerve cells. Dendritic immune recommendations to prevent poliomyelitis in the United States. many Amish are not vaccinated. Typically, the lack of sles virus, which spread to unvaccinated individuals in Case study 1: Questions cells are present in tissues that have contact with the 23/06/16 10:16 am 4. Define post-polio syndrome, and identify who is particularly vulnerable to it. vaccination among the Amish is a reflection of a social the community. Measles virus is the most contagious tradition within the communities related to modern- pathogen of humans. It has an r-nought, or r environment, such as the skin (where they are called 5. Discuss why poliovirus eradiation remains unfinished business. ization rather than religious objection. In 2014, there other words, 1 infected individual is likely to cause 18 These questions relate to the Case Study presented at the laboratory diagnosis of Viral diseases and Working with Viruses in the Research laboratory © Jones & Bartlett6. List Learning,the signs and symptoms of LLC infectious diseases caused by nonpolio enteroviruses.9781284057898_CH08_PASS03.indd© Joneswere 23 measles 361& outbreaks Bartlett in the United Learning, States. The LLC beginning of the chapter. additional cases of measles. Immunology H (MHC II) and Note the importance of emerging enteroviruses, such as enterovirus D68. largest outbreak, which resulted in 383 cases, occurred CHAPTER 7 7. Refresher 342 NOT FOR SALE OR DISTRIBUTION NOTwithin FOR Old1. Order Who SALEis Amish likely the and original Amish OR source Mennonite ofDISTRIBUTION the poliovirus com - munities in contractedKnox County, by the infant Ohio. in 2005? The Knox County eliminated in the United States in 2000, yet spo H cells. Healthy cells will be ignored while cells containing foreign (e.g., measles 2.epidemic An investigation likely startedwas needed afterSee to Case identifytwo StudyAmish potential 1 Questionsmen at radicthe end measles of the epidemics chapter. continue in the United The primary function of major histocompatibility complex (MHC) is to present a sampling of all peptides that were produced in contacts with the infant suffering from poliomy States today. Why is this the case? Explain. a nucleated cell of the body (for MHC I) or that were engulfed by an antigen-presenting cell (for MHC II). (See FiguRE 1.) Case study 1: Poliomyelitis and measles in elitis. Create a list of contacts who should be 11. 30/05/16 10:47 am In 2015, a multistate epidemic of measles occurred - B cells present9781284057898_CH07_PASS04.indd MHC II to get “help” from 342 T interviewed. in the United States that was linked to Disneyland. the amish Community 3. Who is most at risk for contracting OPV-derived - Perform research to summarize who was patient cells infected by viruses) will be attacked by the immune system. It is these peptides that are recognized by T poliomyelitis? Poliovirus and other enteroviruses zero and what factor(s) contributed to the spread cells (MHC I). Processed viral 4. At whatCHAPTER age does the 8 CDC recommend that chil TC Dendritic cell internalizes 362 of measles in multiple states. dren receive the poliovirus vaccine? 12. Measles globally causes an estimated 400 deaths and processes viral antigens 5. Explain why OPV was discontinued in the United In July 2005, a 7-month-old unvaccinated Amish each day. Perform research. List countries in Viral antigen © Jones & Bartlett Learning, LLCStates. © Jones & Bartlett Learning, LLC infant girl was hospitalized in a central Minnesota hos- - which measles is . Of the countries listed, 6. About 30% of reported measles cases have one or CD8 pital because she was failing to thrive. The child suf- what countries are the top three most-visited more complications. List the complications of mea fered from diarrhea and NOTrecurrent infections. FOR She was SALE OR DISTRIBUTION9781284057898_CH08_PASS03.indd 362 NOTcountries FOR by international SALE tourist arrivals basedOR on DISTRIBUTION sles and the percentage of cases that experience placed in isolation and evaluated for a bone marrow estimates by the United Nations World Tourism Interleukin-4 them. Complications are most common in what transplant after the results of medical laboratory tests Organization (UNWTO)? age group? ( 13. indicated she was severely immunocompromised. - Religious concerns and vaccination have a long Boost Infected cines/pubs/pinkbook/meas.html#vaccines.)Hint: See http://www.cdc.gov/vac history. Perform research and cite at least five CD4 Meanwhile, experts at the Minnesota Department B cells MHC I body cell 7. The R examples of vaccine-preventable epidemics among Clone of of Health (MDH) isolated an enterovirus from the 0 of measles is 18. There were about 3,500 Amish© Teri Shors. in Knox County in 2014. What proportion xic TC girl’s stool sample. The enterovirus was identified as a - religious schools, congregations, and communi cytoto of Amish would need to be vaccinated to stop the ocessed Cytolytic vaccine-derived poliovirus. The genomic sequence of ties. (Hint Pr spread of measles cases? Use the formula (1 – Goal : See Grabenstein, 2013.) Boost TC viral antigens granules the enterovirus, however, was determined to be 2.3% References R0)/Current R (perforins, different from the parent Sabin poliovirus type 1 strain, Amish do not object to vaccination, but significant - Figure 1 should be 1. An0 R to determine this. The Goal R Anderson, V. L. 2015. “Promoting childhood .” and it was estimated that it was replicating for about granzymes) pockets of lower vaccination rates may exist in Amishstable communities. or not spreading. J Nurse Pract 11:1–10. H MHC II Viral peptide © Jones2 years & in an Bartlett immunocompromised Learning, individual. Oral LLC 0 of 1© means Jones that the infection is& BartlettBahta, L., et al. 2005. “PoliovirusLearning, infections in four unvacci LLC- Boost T 8. Explain why the following statement is true: “ TH poliovirus vaccine (OPV) is still widely used in most 0 nated children—Minnesota, August–October 2005.” higher the R T- countries, but it has not been used in the United States MMWR 54:1–3. Boost NOT FOR SALE OR DISTRIBUTIONcontracted measles while on a mission trip to the Phil0, -the higher NOTthe number of vaccinationsFOR SALE OR DISTRIBUTION ). Amish or Hutterite needed to stop the spread of an infectious disease Feikin, D., et al. 2014. “Measles—United States, January APCs receptor since 2000 and in Canada sinceFigure 1997. 1 ippines. The men returned to the United States and Old Order Amish and Amish Mennonite views about the formula in question 7 to support your answer.The 1–May 23, 2014.” MMWR 63:496–499. thought they had dengue fever, whichShow is yournot contacalculations.- Goodson, J., and Seward, J. F. 2015. “Measles 50 years after vaccination vary widely ( gious. They attended church to pray9. forExplain a fast the recovery. relationship between herd immunity.” Use use of measles vaccine.” Infect Dis Clin N Am 29:725–743. and death of virally religious doctrine does not prohibit vaccination, but Instead, Amish at the church were exposed to the mea- Grabenstein, J. D. 2013. “What the world’s religions teach, infected cell and R 0, of 18. In many Amish are not vaccinated. Typically, the lack of 0. applied to vaccines and immune globulins.” Vaccine sles virus, which spread to unvaccinated10. The measles individuals vaccine in has been available in the vaccination among the Amish is a reflection of a social 31:2011–2023. the community. Measles virus is Unitedthe most States contagious since 1963 and measles cases were Roberts, L. 2005. “Minnesota polio case stumps experts.” Sci- tradition within the communities related to modern- pathogen of humans. It has an , or r-nought r ence 310:213. Antigen-presentingTH (Tcell helper activate: cells) ization rather than religious objection. In 2014, there other words, 1 infected individual is likely to cause 18 Thompson, K. M., and Kisjes, K. H. 2015. “Modeling measles C cells ( cytotoxic T ). T (cytotoxic T-lymphocytes) were 23 measles outbreaks in the United States. The additional cases of measles. transmission in the North American Amish and options for C 215 outbreak response.” Risk Anal. doi:10.1111/risa.12440. H cells (T helper cell) and T mmunity) largest outbreak, which resulted in 383 cases, occurred innate i © Jones & Bartlett Learning,within Old Order Amish LLC and Amish Mennonite com- © Jones & Bartlett Learning, LLC efenses ( munities in Knox County, Ohio. The Knox County 1 Antigen-presenting cells activate T See Case Study 1 Questions at the end of the chapter. FiguRE nonspecific Host d NOT FOR SALE OR DISTRIBUTIONmeasles epidemic likely started after two Amish men NOT FOR SALE OR DISTRIBUTION nvaders: 16/06/16 5:04 pm 30/05/16 10:47 am efenses Against viral i 5.2 Host d Poliovirus and other enteroviruses CHAPTER 8 362 xvi Preface © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. 9781284057898_CH08_PASS03.indd 362

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30/05/16 10:48 am ChaPter 8 Virus Files—The Virus Files within each © Jones & Bartlett Learning, LLC © Jones & Bartlettchapter Learning, connect chapter LLC topics to current NOT FOR SALE OR DISTRIBUTION NOT FOR SALEresearch OR DISTRIBUTION or virology techniques. Development of a Rapid Test to Determine Whether Respiratory illnesses ViRus filE 7-2 Are Caused by a Virus or Bacterium Poliovirus and Other Enteroviruses

All too often a person shows up at a clinic or hospital emergency room suffering from symptoms of a “ The fight against respiratory tract infection and the© doctor Jones prescribes antibiotics& Bartlett just in case the Learning, patient is suffering from LLC © Jones & Bartlett Learning, LLC infantile paralysis is a a bacterial infection. Antibiotics will not work if a virus is the cause of the illness. Symptoms alone are fight to the finish, and the not enough to diagnose a respiratoryNOT infection. FOR Today, SALEif it is influenza OR season DISTRIBUTIONa rapid test may be done to NOT FOR SALE OR DISTRIBUTION . terms are unconditionalsurrender ” determine whether the patient is suffering from influenza A or B or strep throat caused by the bacterium Streptococcus pyogenes. A group of researchers at Duke University are developing a rapid blood test that can distinguish whether —Franklin Delano Roosevelt, 32nd U.S. president and a respiratory illness is caused by a viral or bacterial pathogen. In order to develop the test, small studies polio survivor (1944) were done using healthy volunteers who). The agreed Duke to be infected with different strains of influenza A virus. iguRE 1 Draped over the handlebars of a Their blood was drawn during the course of infec- bicycle in the Central African tion and genetically analyzed (f country of Chad is a satchel © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC containing poliovirus vaccine. The researchers discovered that the expression of 30 satchel includes a logo with the NOTcellular FOR genes involved SALE in the immune OR response DISTRIBUTION NOT FOR SALE OR DISTRIBUTION words “Kick Polio out of Africa.” The were turned on in different ways during the viral bicycle is used as transportation to deliver poliovirus vaccine to out-of- infection. The cellular immune response was the-way villages that are far from referred to as a specific viral or genetic signature. more urbanized areas of the country. The global effort to eradicate polio is When infected by a virus, a person’s immune the largest public health initiative in system responds differently than it would when

human history. It began in 1988 by H. M.P. Kurnit, CDC/Molly the of Courtesy fighting a bacterial infection. The researchers the WHO with the goal of eradicating polio by the yearnot 2000. been This met goal to date.has developed an RT-PCR test to detect the viral Poliovirus Eradication is unfi nished © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 8.10 signature of influenza A viruses in patient blood O U t L i n e Business samples. Other Enteroviruses (Nonpolio Viruses) NOT FOR SALE ORThe DISTRIBUTION viral signatures of the volunteers infected NOT FOR SALE OR DISTRIBUTION 8.11 Brief Overview of Enteroviruses Myocarditis and Dilated Cardiomyopathy with influenza A viruses were compared to blood 8.1 Langerhan’s cells); mucous membranes; and the lin- The History of Polio Respiratory Enteroviruses: Rhinoviruses samples collected from people whoing wentof the to nose, lungs, and gastrointestinal tract. Medi- 8.2 Triggering Asthma Clinical Features of Poliomyelitis hospital emergency rooms complainingcal graduate of fever student Paul Langerhan, who was working 8.3 Enteroviruses 71 and D68: Reemerging and respiratory illness. Their rapidunder blood thetest mentorship of Professor Rudolf Virchow at Post-Poliomyelitis Syndrome α defensins have been shown to block infection Viral Pathogens? The identified positive viral signaturesthe or Instituteinfections of in Pathology of the University of Berlin in Classifi cation and Structure of Poliovirus 8.4 of different naked viruses by such89% mechanisms of the cases as and the correctly ruled1868, out first nega- described Langerhan’s cells. In his 1868 land- Summary Stability of Enteroviruses in the Environment aggregation or clumping of naked tiveviruses cases on 94% the surfaceof the time. Earlymark differentiation paper, “Uber die Nerven der menslichen Haut,” resources © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC laboratory Diagnosis of Poliovirus of host cells (e.g., BK viruses are inhibited this way), the Langerhan described the cells as nerve endings ofCourtesy the of Amanda Mills/CDC. 8.5 Poliomyelitis and Measles in the between viral and bacterial- respiratory infec- infections Case Study 1: inhibition of viral uncoating (e.g., human adenoviruses), skin. In 1882 he corrected his interpretation, stating, “I tions can directNOT treatment FORappropriately SALE (e.g., OR DISTRIBUTION- NOT FOR SALE OR DISTRIBUTION Cellular Pathogenesis Amish Community and by blocking the viral genome from entering the am now convinced that my cells are in no way essential). Den Echovirus 4 Tamiflu for influenza A patients who are at high Test tube rack containing purple-capped- blood 8.6 iguRE 1 Poliovirus replication Case Study 2: nucleus of its host cell (e.g., humanrisk papillomaviruses). for complications of influenzafor Anerve infection). endings.” f Refresher: Immunology 8.7 Creating Poliovirus in a Test Tube β defensins block enveloped viruses such as respira MHC class I andcollection II molecules tubes. In are the expressed future, blood on may the be analyzed for ViruS FilE 8-1: The Treatments Using Google Earth to Track Poliovirus It can curb the misuse of antibiotics or improve protein profiles of immune system genes 5-6 expressed). during 8.8 tory syncytial virus and human parainfluenza virus type surfaces of dendritic cells (see FiguRE ViruS FilE 8-2: triage in settings of a potential pandemic. The infection for diagnostic purposes. Prevention 3 from viral entry into host cells by interacting directly dritic cells act as scouts that are very efficient at identify 8.9 down the Congo River development of this rapid diagnostic assay and Chemicals and Gamma Globulin with them. The defensins disrupt defensins the viral inhibit envelope, herpes ing foreign invaders such as viruses and bacteria, even and β its testing in a “real-world” patient setting are Inactivated Vaccines inactivating the virus’s infectivity (i.e., ability to enter when they are present in minute numbers ( H cells are into host cells). Both α paving the way for establishing thisDendritic new type cells of internalize the pathogen,H cells. digest (T it, and The Cutter Incident 361 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC simplex virus (an enveloped virus)diagnostic by blocking testing in thethe clinic. display or present the foreign peptides on their surface Live, Attenuated Poliovirus Vaccines cellular receptor present on the surface of its host cell, using the MHC II molecules to T NOT FORReferences SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION preventing entry into the host cell.Ramilo, O., et al. 2007. “Gene expression describedpatterns in blood later leukocytes in this discriminate chapter patterns as part with of acute the infections.” discussion Blood 109:2066–2077. 30/05/16 10:47 am Zaas, A. K., et al. 2013. “A host-based RT-PCRon specific gene expression immune signature defenses.) to identify Activatedacute respiratory dendritic viral infection.” cells Sci Transl Med Refreshers—Reviews are presented to Dendritic cells 5:203ra126. also express high levels of another surface receptor, B7, provide students the opportunity to brush dendritic cells are covered with long, spiky arms that resemble the dendrites of nerve cells. Dendritic immune up on important biological concepts. cells are present in tissues that have contact with the 23/06/16 10:16 am environment, such as the skin (where they are called

laboratory diagnosis of Viral diseases and Working with Viruses in the Research laboratory 9781284057898_CH08_PASS03.indd 361 © Jones & Bartlett Learning, LLC © Jones (MHC II)& and Bartlett Learning, LLC ImmunologyCHAPTER 7 H NOT FOR RefresherSALE OR342 DISTRIBUTION NOT FOR SALE OR DISTRIBUTION cells. Healthy cells will be ignored while cells containing foreign proteins (e.g., The primary function of major histocompatibilityH complex (MHC) is to present a sampling of all peptides that were produced in a nucleated cell of the body (for MHC I) or that were engulfed by an antigen-presenting cell (for MHC II). (See FiguRE 1.) B cells present9781284057898_CH07_PASS04.indd MHC II to get “help” from 342 T cells infected by viruses) will be attacked by the immune system. It is these peptides that are recognized by T TC cells (MHC I). Dendritic cell internalizes Processed viral antigens and processes viral antigens © Jones & Bartlett Learning,Viral antigen LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONCD8 NOT FOR SALE OR DISTRIBUTION Interleukin-4

Boost CD4 Infected B cells MHC I body cell Clone of C cytotoxic T lytic Processed Cyto Boost TC viral antigens granules (perforins, granzymes) MHC II © JonesBoost TH & Bartlett Learning,Viral peptide LLC © Jones & Bartlett Learning, LLC TH Boost T- lymphocyte NOT FORAPCs SALEreceptor OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Lysis and death of virally infected cell

Antigen-presentingTH (Tcell helper activate: cells) C cells ( cytotoxic T lymphocytes). T (cytotoxic T-lymphocytes) C 215 H cells (T helper cell) and T mmunity) innate i © Jones & Bartlett Learning, LLC © Jonesefenses ( & Bartlett Learning, LLC 1 Antigen-presenting cells activate T FiguRE nonspecific Host d NOT FOR SALE OR DISTRIBUTION nvaders: NOT FOR SALE OR16/06/16 DISTRIBUTION 5:04 pm efenses Against viral i 5.2 Host d

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High-Quality, Carefully Rendered Illustrations and Electron micrograph of filamentous-shaped CTV isolated from an infected plant. The particles are approximately 2,000 nm © Jones & Bartlett Learning, LLC Figure 19-24 © Jones & Bartlett Learning, LLC Figures—Over 500 NEW and revised photos and in length. - NOT FOR SALE OR DISTRIBUTION NOTillustrations FOR SALE are OR included DISTRIBUTION in this edition, includ- are used to diagnose diseases caused by plant viruses. The major means of control (depending on the disease) b ing a number of unique photographs taken by the Summary include chemical or biological control of insect vectors, - removal of alternate hosts (e.g., weeds), sanitation tech E. coli author to depict research methods, historical per- , a botanist, is credited with coining niques (e.g., cleaning of farm implements and proper a + Phage the term virus while studying TMV-infected tobacco grafting techniques), use of certified virus-free seed or 2 spectives, or current topics described in the text. plants during the late 1800s. Even though the first virus stock, growth of resistant crop varieties, and plant quar E. coli to be discovered was tobacco mosaic virus (TMV), plant + antines to prevent disease establishment in areas where viruses are not nearly as well understood as their animal it does not occur (material is grown or kept isolated for Phage Phage containing 1 © Jones35S-labeled & proteinBartlett (red) Learning, LLC © Jones & Bartlett Learning, LLC counterparts. Plant viruses continue to be a major threat longer periods for observation to determine absence of infects nonradioactive cell. in the production of vegetable and ornamental crops disease or pest), and testing. These procedures are time- E. coli worldwide. Their control remains a major challenge in consuming and costly and require skilled professionals. bacteria Phage containing Advances in control of viral plant diseases are 32 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION the 21st century. P-labeled DNA (green) Nasal infected with The infection of plant cells is not achieved by surface focused on creating natural (breeding) and engineered labeled infects nonradioactive cell. cavity phages E. coli host receptors—a major difference between viral infections resistance to plant viruses. DNA Ar tery of plants as opposed to animals. Plant viruses require a The majority of plant viruses are naked, helical- Upper Alveolus break in the cell wall for entry and are transmitted in a shaped +ssRNA viruses. Instead of having segmented Respiratory Bronchiole number of different ways, including mechanical means E. coli host Mouth genomes like influenza A virus, some plant viruses have Centrifuge Tract (oral cavity) (i.e., human and environmental damage), soil trans- multipartite genomes in which the genome consists of mission, vegetative propagation (grafting), piercing and more than one molecule of nucleic acid, but each genome chewing insects and other vectors, seed transmission, molecule is packed into a separate virus particle. Thus, Vein - Centrifuge and pollen transmission. all discrete virus particles must enter the cell to establish © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC The majority of plant viruses are transmitted by a productive infection. - Phage heads insect vectors (e.g., aphids, leafhoppers, plant-hoppers, Viruses spread short distances (from cell to cell) Ms. Chase’s are removed Red Larynx beetles, mites, mealybugs, whiteflies, and thrips). Symp with the aid of movement proteins that “channel” them NOT FOR SALE OR blenderDISTRIBUTIONin supernatant. NOT FOR SALE OR DISTRIBUTION bacteriophage toms of viral plant diseases vary from mild to severe but proteins Trachea through the plasmodesmata. Channeling occurs without Phage heads rarely kill the plant. Symptoms may include dwarfing causing cellular lysis. A systematic (long distance) infec Ms. Chase’s - are removed Phage or stunting of plants, leaf curling, reduced yield, fruit tion of the plant occurs if plant viruses are transported blender in supernatant. Infected cell - DNA (green) distortion, chlorosis (yellowing), other color deviations inside of cells remains in Capillary longer distances through the vascular system by the Infecting precipitate. net (e.g., variegation of flower petals), “mosaic” patterns on phloem. nonlabeled DNA work leaves, ring-shaped spots on leaves, wilting and wither Plants do not have an “active” immune system Infected cell ing, necrosis (black or grayish brown discoloration due analogous to humans, such as the production of anti remains in Progeny phages form; Infecting precipitate. cell lyses. to the death of cells and tissues), or bark scaling. bodies to combat pathogens. Plants do, however, possess labeled DNA In addition to symptomatic observations, methods © Jones & Bartlett Learning, LLC Progeny phages © Jones & Bartlett Learning, LLC used to detect and identify plant viruses are similar Progeny phages form; contain almost no 23/06/16 10:56 am cell lyses. 35S-labeled protein. to those used in detecting animal viruses. Infectivity NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTIONLung assays, ELISAs, electron microscopy, and RT-PCR or PCR Progeny phages Plant Viruses contain some 32P-labeled DNA. Chapter 19 822 Lowe Respiratoryr Te Conclusion: Mainly DNA, not protein, is inherited from parental phage. Right rminal Tract 9781284057898_CH19_PASS02.indd 822 bronchiole bronchus Left bronchus © JonesHost & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Host NOT FORserum SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION glycoproteins proteins Protease (p10) Lys Host tRNA

Integrase (p32) © Jones & Bartlett Learning,Host LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONICAM-1 NOT FOR SALE OR DISTRIBUTION Host CypA gp120 Matrix gp41 (p17) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC vpr +ssRNA NOT FOR SALE OR DISTRIBUTIONp24 NOT FOR SALE OR DISTRIBUTION rse Reve (nucleocapsid) transcriptase (p66) Courtesy of James Gathany/CDC.

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Chapter Summary—A synopsis of the key Electron micrograph of filamentous-shaped CTV isolated from an infected plant. The particles are approximately 2,000 nm Figure 19-24 © Jones & Bartlett Learning, LLC © Jonesin length.& Bartlett Learning, LLC points is provided at the end of each - NOT FOR SALE OR DISTRIBUTIONare used to diagnose diseases caused by plant viruses.NOT FOR SALE ORchapter. DISTRIBUTION The major means of control (depending on the disease) Summary include chemical or biological control of insect vectors, - removal of alternate hosts (e.g., weeds), sanitation tech Martinus Beijerinck, a botanist, is credited with coining niques (e.g., cleaning of farm implements and proper the term virus while studying TMV-infected tobacco grafting techniques), use of certified virus-free seed or plants during the late 1800s. Even though the first virus stock, growth of resistant crop varieties, and plant quar to be discovered was tobacco mosaic virus (TMV), plant antines to prevent disease establishment in areas where viruses are not nearly as well understood as their animal it does not occur (material is grown or kept isolated for counterparts. Plant viruses continue to be a major threat longer periods for observation to determine absence of in the production of vegetable and ornamental© Jones crops &disease Bartlett or pest), and testing. Learning, These procedures are time- LLC © Jones & Bartlett Learning, LLC worldwide. Their control remains a major challenge in consuming and costly and require skilled professionals. the 21st century. NOT FOR SALEAdvances in controlOR ofDISTRIBUTION viral plant diseases are NOT FOR SALE OR DISTRIBUTION The infection of plant cells is not achieved by surface focused on creating natural (breeding) and engineered receptors—a major difference between viral infections resistance to plant viruses. of plants as opposed to animals. Plant viruses require a The majority of plant viruses are naked,CAsE helical- sTudy 2: QuEsTions break in the cell wall for entry and are transmitted in a shaped +ssRNA viruses. Instead of having segmented number of different ways, including mechanical means genomes like influenza A virus, some plant viruses have - References (i.e., human and environmental damage), soil trans- multipartite genomes in which the genome consists of Hinton, M. G., et al. 2015. “West Nile virus activity in a winter mission, vegetative propagation (grafting), piercing and roost of American crows (Corvus brachyrhynchos): Is bird-to- - more than one molecule of nucleic acid, but each genome bird transmission important in persistence and amplifica- chewing insects and other vectors, seed transmission, molecule is packed into a separate virus particle. Thus, Journal of Medical Entomology 52:683–692. - 1. Perform research to determine the structural char tion?” and pollen transmission. all discrete virus particles must enter the cell to establish Ip, H. S., et al. 2014. “West Nile virus transmission in winter: ©The Jones majority of plant & viruses Bartlett are transmitted Learning, by LLCacteristics of WNV (e.g., size, shape, presenceHint :or ©See Jones & Bartlett Learning, LLC a productive infection.absence of envelop). What type of nucleic acid ResourcesThe 2013 Great— SaltUnderstanding Lake bald eagle and eared grebes Viruses mor is grounded Viruses spread short distances (from cell to cell) - tality event.” PLoS Currents 18:6. insect vectors (e.g., aphids, leafhoppers, plant-hoppers, genome does it have? How many genes? What beetles, mites, mealybugs, whiteflies, and thrips). Symp in evidence.McLean, R. G. 2006. Resources “West Nile virus in North provided American birds.” for reference NOT FOR SALE OR DISTRIBUTIONwith the aid of movementfamily proteins of virusesthat “channel” does it thembelong to? ( NOT FOROrnithological SALE Monographs 60:44–64. OR DISTRIBUTION toms of viral plant diseases vary from mild to severe but through the plasmodesmata. Channeling occurs without http://viralzone.expasy.org/.) Nemeth, N., et al. 2006. “Natural and experimental West Nile rarely kill the plant. Symptoms may include dwarfing causing cellular lysis. A systematic (long distance) infec have beenvirus infection separated in five raptor species.” byJournal category of Wildlife Dis- into Primary - 2. Most humans (about 80%) infected with WNV or stunting of plants, leaf curling, reduced yield, fruit tion of the plant occurs if plant viruses are transported eases 42:1–13. have no symptoms. What kind of -laboratory test(s) - distortion, chlorosis (yellowing), other color deviations longer distances throughmight the youvascular ask for system if you by want the to know whetherLiterature, Nemeth, N., et Reviews, al. 2009. “Clinical evaluation Popular and outcomes Press, of and Video (e.g., variegation of flower petals), “mosaic” patterns on naturally acquired West Nile virus infection in raptors.” phloem. you have been infected with WNV? Journal of Zoo and Wildlife Medicine 40:51–63.Journal of Wildlife Diseases leaves, ring-shaped spots on leaves, wilting and wither Plants do not have an “active” immune system Productions, so that students can easily find 3. WNV is transmitted by mosquito bites and by eat Saito, E. K., et al. 2007. “Raptor mortality due to West Nile ing, necrosis (black or grayish brown discoloration due analogous to humans, suching infected as the production birds. Perform of anti a PubMed search and virus in the United States, 2002.” to the death of cells and tissues), or bark scaling. bodies to combat pathogens. Plants do, however, possess the type43:206–2013. of information they are interested In addition to symptomatic observations, methods list other viruses that can be transmitted through mosquito bites and by consumption. © Jones & Bartlettused to detect Learning, and identify plant viruses LLC are similar © Jones & Bartlettin delving Learning, into. LLC 4. How many different mosquito23/06/16 species 10:56 inam the to those used in detecting animal viruses. Infectivity United States: Seecan behttp://www.cdc.gov/westnile infected with WNV? Create a NOT FOR SALEassays, OR ELISAs, DISTRIBUTION electron microscopy, and RT-PCR or PCR list. (HintNOT FOR SALE OR DISTRIBUTION Plant Viruses /transmission/.) Chapter 19 822 5. What other species of birds besides eared grebes and crows can be infected with WNV? Create Hint: See http://www.cdc.gov/westnile a list. ( /transmission/.) - 9781284057898_CH19_PASS02.indd 822

Trends in Hulo, C., et al. 2011. “ViralZone: A knowledge resource to under © Jones & standBartlett virus diversity.” Nucleic Learning, Acids Research 39:D576–D582. LLC © Jones & Bartlett Learning, LLC Hurst, C. J., Benton, W. H., and Enneking, J. M. 1987. “Three- La Scola, B., et al., 2008. “The as a unique parasite of dimensional model of human type 14.” the giant Mimivirus.” Nature 455:100–104. NOT FOR SALEBiochemical Sciences OR 12:460. DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Raoult, D., et al.Science 2004. 306:1344–1350.“The 1.2 megabase genome sequence of Resources La Scola, B., et al. 2010. “Tentative characterization of new envi- Mimivirus.” Jaiasvuori, M., et al. 2015. “Chasing the origin of viruses: - ronmental giant viruses by MALDI-TOF mass spectrometry.” forming genes as a life-saving preadaptation within a commu- Intervirology 53:344–353. Rota, P. A., et al. 2003. “Characterization of a novel nity of early replicators.” PLoS ONE e0126094. associated with severe acute respiratory syndrome.” Science Primary Literature Lagier, J.-C., et al. 2012. “Microbial culturomics: Paradigm shift in 300(5624):1394–1399. Koonin, E. V. 2005. “Virology: GulliverBarry, among M., the et Lilliputians.”al. 2014. “Ebola outbreak in Conakry, Guinea: Epide- the human gut microbiome study.” Clinical Microbiology and Current Biology 15(5):167–169. miological, clinical, and outcome features.” Medicine et maladies Infection 18:1185–1193. Simon, J. A., et al. 2013. “A strategy to estimate unknown viral Koonin, E. V., and Doija, V. V. 2014. “Virus worldinfectieuses as an 44:491–494. evolution- diversity in mammals.” mBio 4:e00598. - Legendre, M., et al. 2012. “Genomics of and the elusiveProceed - ary network of viruses and capsidless selfish elements.”Micro- fourth domain of life.” Communicative & Integrative Biology Susan-Monti, M., et al. 2007. “Ultrastructural characterization of Biagina, P., et Newal. 2012. England “Variola Journal virus of Medicine in 300-year-old 367:2057–2059. Siberian biology and Molecular Biology Reviews 78:278–303.mummy.” 5:102–106. the giant volcano-likePLoS ONE virus 2:e328. factory of Acanthamoeba polyphaga Mimivirus.” Legendre, M., et al. 2012. “Genomics of MegavirusCohen, G., and et al.,the 2011.elusive “Ameobae-associated keratitis, France.” Legendre, M., et al. 2015. “In-depth study of sibericum, a fourth domain of life.” CommunicativeEmerging & Integrative Infectious Biology Diseases 17:1306–1308. new 30,000-y-old giant virus infecting Acanthamoeba.” ©Woolhouse, Jones PhilosophicalM., et al. 2012. Transactions& “Human Bartlett ofviruses: the Royal Discovery Society B: and Learning,Biological emer 5:102–106. LLC © Jones & Bartlett Learning, LLC gence.” Foy, B. D., et al. 2011. “Probable non--borne transmission ings of the National Academy of Sciences 112:e5327–e5335. Sciences 367:2864–2871. Virus Genes 48:218–223. Lipkin, W. I., and Firth, C. 2013. “Viral surveillanceof Zika and virus, discovery.” Colorado, USA.” Emerging Infectious Diseases Marco, A. M., et al. 2003. “The genome sequence of the SARS- Current Opinion in Virology 3:199–204. 17:880–882. associated coronavirus.” Science 300:1399–1404. NOTYoosuf, N., etFOR al. 2013. “Complete SALE genome sequence OR of Courdo11 DISTRIBUTION NOT FOR SALE OR DISTRIBUTION virus, a member of .” Lowenstin, E. J. Journal2004. “Paleodermatoses: of the AmericanHall, Academy Lessons R. J., et oflearned al.Dermatology 2014. from “Evaluation of rapid and simple techniques Mlakar, J., et al. 2016. “Zika virus associated with microcephaly.” mummies.” for the enrichment of viruses prior to metagenomics virus dis- New England Journal of Medicine [Epub ahead of print]. Yutin, N., et al. 2013. “, polintons, and transpovirons: 50:919–936. Journal of Virological Methods 195:194–204. A complex evolutionary network of diverse selfish genetic ele- covery.” Ogata, H., Raoult, D., and Claverie, J. M. 2005. “A newJournal example of Infec - ments with different strategies.” Virology Journal Marano, G., et al. 2015. “Zika virus and theIoos, never-ending S., et al. 2014.Medecine story “Current of et maladies Zika virus infectieuses epidemiology 44:302–307. and recent of viral intein in Mimivirus.” Virology 2(1):8. emerging pathogens and transfusion medicine.” Blood Transfu- 10:158. epidemics.” Popgeorgiev, N., et al. 2013. “-like virus recovered sion 5:1–6. Kuhn, J. H.,Mimiviridae et al. 2014. and “Nomenclature- and database-compatible from blood donated by asymptomatic humans.” Matthews, R. E. F. 1985. “Viral taxonomy fornames the non-virologist.” for the two Ebola virus variants that emerged in Guinea tious Diseases 208:1042–1050. Annual Review of Microbiology 39:451–474. Reviews and the Democratic Republic of Congo in 2014.” Viruses Popgeorgiev, N., et al. 2013. “Marseillevirus adenitis in an Abergel, C., et al. 2015. “The rapidly expanding universe of giant Pagnier, I., et al. “A decade of improvements6:4760–4799. in 11-month-old child.” Journal of Clinical Microbiology 51:97 viruses: Mimivirus, , and Mollivirus.” isolation from amoebae.” Intervirology 56: 4102–4105. La Scola, B., et al. 2003. “A giant virus in amoebae.” Science Resources FEMS Microbiology Reviews 39:779–796. 354–363. 299:2033. © Jones & BartlettAdams, M. Learning,J., Antoniw, J. F., and Kreuze, LLCJ. 2009. “: A Pearson, H. 2008. “‘Virophage’ suggests© LavirusesJones Scola, are B., alive.” et al. Nature 2005.& “MimivirusBartlett in pneumonia Learning, patients.” LLC new family of rod-shaped plant viruses.” Archives of Virology 454(7): 677. Emerging Infectious Diseases 11:449–452. 16/06/16 4:30 pm 154:1967–1972. Petersen, E. E., et al. 2016. “Interim guidelines for pregnant NOT FOR SALE OR DISTRIBUTION women during a Zika virus outbreak—UnitedNOT FOR States, 2016.” SALE OR DISTRIBUTION Anthony, S. M., et al. 2015. “Filoviruses: One of these things is ASM (not) like the other.” Viruses 7:5172–5190. - Morbidity and Mortality Weekly Report 65:30–33. Bogoch, I. I., et al. 2016. “Anticipating the international spread of Racanielle, V. R. 2010. “Social media and microbiology education.” Zika virus from Brazil.” Lancet 387:335–336. PLoS Pathogens 6:e1001095. Boyer, M., et al. 2009. “Giant Marseillevirus highlights the role of Raoult, D. 2005. “The journey from to Mimivirus.” amoebae as Proceedingsa melting pot of in the emergence National ofAcademy chimeric of microor Sciences News 71(6):278–284. ganisms.” Raoult, D., and Forterre,Nature Reviews P. 2008. Microbiology “Redefining 6:315–319. viruses: Lessons from doi/10.1073/pnas.0911354106. Mimivirus.” 9781284057898_CH02_PASS03.indd 97 Carrillo-Tripp, M., et al. 2009. “VIPERdb2: An enhanced and web Rossman, M. G., et al. 1987. “ viruses.” Trends in API enabled relational database for structural Virologyvirology.” 466–467: Nucleic Biochemical Sciences 12:313–318. Acids Research 37:D436–D442. Sobhy, H., et al. 2015. “Identification of giant Mimivirus protein Chelikani, V., et al. 2014.© “Revisiting Jones the genome & packaging Bartlett in functions Learning, using RNA interference.” LLC Frontiers in Microbiology © Jones & Bartlett Learning, LLC viruses with lessons from the ‘Giants.’” 6:345. 15–26. NOT FOR SALE ORvan Regenmortel, DISTRIBUTION M. H. V., and Mahy, B. W. 2004. “Emerging NOT FOR SALE OR DISTRIBUTION Ciu, C. Y. 2013. “Viral pathogen discovery.” Current Opinion in issues in virus taxonomy.” Emerging Infectious Diseases Microbiology 16:468–478. 10(1):8–13. Additional Online Study Tools—Practice Claverie, J.-M.,Annual and Review Abergel, of Genetics C. 2009. 43:49–66. “Mimivirus and its viro- Zandi, R., et al. 2004. “Origin of icosahedral symmetry in viruses.” phage.” Proceedings of the National Academy of Sciences 101(44): activities and prepopulated quizzes Claverie, J.-M., et al. 2006. “Mimivirus and the emerging concept 15556–15560. of ‘giant’ virus.” Virus Research 117:133–144. are available for self-study. Claverie, J.-M., et al. 2009. “Mimivirus and Mimiviridae: Giant Popular Press viruses with an increasing number of potential hosts, including corals and sponges.” Journal of Invertebrate Pathology 101: Brantly, K., and Brantly, A., with David Thomas. 2015. Called for Life: How Loving Our Neighbor Led Us into the Heart of the Ebola 172–180. Epidemic. Colorado Springs: Waterbrook Press. Durzynska, J., and Gozdzicka-Jozefiak, A. 2015. “Viruses and cells © Jones intertwined& Bartlett since the dawn ofLearning, evolution.” Virology Journal LLCGarrett, L. 2014. Ebola: Story of an Outbreak. New York: Hachette© Jones & Bartlett Learning, LLC Books. 12:169. Iezzoni, L., and McCullough, D. 1997. Influenza, 1918: The Worst NOT FOREberhard, SALE M.Emerging 2004. “VirusInfectious ORtaxonomy: Diseases 10:153–154. OneDISTRIBUTION step forward, two steps Epidemic in American History. New York: TV Books. NOT FOR SALE OR DISTRIBUTION back.” Kehret, P. 1996. Small Steps: The Year I Got Polio. Morton Grove, IL: Forterre, P. 2013. “The great virus comeback.” Biologie Aujourd’hui Albert Whitman. 207:153–168. [Article in French] Ghedin, E., and Claverie, J.-M. 2005. “Mimivirus relatives in the Sargasso Sea.” Virology Journal 2:62. Hayes, E. B. 2009. “Zika virus outside of Africa.” Emerging Infectious Diseases 15:1347–1350.

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9781284057898_FMxx_00i_xxiv.indd 20 04/07/16 9:12 am Ebola Case Study—This NEW and appendix C © Jones unique& Bartlett in-depth Learning, analysis LLC of the © Jones & Bartlett Learning, LLC modern Ebola outbreak is perfect NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Case study: Combating the Worst epidemiC for classroom discussion. It is fully of ebola Virus disease in human history illustrated and includes over 50 Case Study Questions and a com- Patient Zero

During March 2014, blood samples collected from 20 plete Resources section. Ebola patients hospitalized in Gueckedou, Macenta, and Kis- reservoir. Bats can survive Ebola infection. In a © Jones & Bartlett Learning,sidougou, LLC Guinea, were shipped to Biosafety Level-4 frustrating© Jones twist, the tree & the Bartlett children played at Learning,was LLC (BSL-4) laboratories in Lyon, France, and Hamburg, burned to the stump just before researchers arrived to NOT FOR SALE OR DISTRIBUTIONGermany, for virology testing. Nearly all of the patients gatherNOT bats for FORsamples for testing.SALE Villagers OR said that DISTRIBUTION (84%) had died from a mysterious illness character when the tree was burning there was a “rain of bats.” The hollow tree was only 50 meters (54 yards) from the ized by fever, severe diarrhea, and vomiting. re house where the boy lived. The first individuals infected transcriptase polymerase chain reaction (rt-pCr) kits were used to screen the blood plasma for Old World arenavi- by Ebola viruses were women and children, rather than - hunters. It is possible that the toddler was infected when ruses and Lassa virus. None of the samples were positive for verse- playing in the tree with an infected bat or by ingesting Lassa virus. a small quantity of bat droppings that contained Ebola The viral RNA was extracted from patient blood plasma, and commercial RT-PCR kits viruses. detect the nucleotide sequences of the conserved region Epicenter of the Ebola Outbreak in West Africa © Jones & Bartlett Learning, LLC of the Ebola virus L © Jones & Bartlett Learning, LLC were used to The child’s sister, mother, and grandmother; a village RNA polymerase) using gene PCR (which primers codes designed for Ebolato amplify virus NOT FOR SALE OR DISTRIBUTION genes of known Ebola virus species NOT( FORmidwife; SALE and the ORnurse who DISTRIBUTION cared for them became dibugyo infected and suffered from similar symptoms, in addi- , Ravn Tai Forest tion to bleeding. Between December 29, 2013, and January ). Additional , Reston Sudan 25, 2014, all of them died. The villagers were frightened amplify and detect the GP , Lloviu kits were used, to real-time RT-PCR , MarburgBun- virus surface glycoprotein [GP]) or the , and codes for the viral nucleoprotein) gene (whichto detect codes Ebola for virus. Ebola See fi gure 1 for the structure of Ebola virus.NP gene The (whichcom mercial kits confirmed that 15 of the 20 patients were RNA positive for Ebola virus based on detection of the L factor VP30 Ebola viruses were detected in the serum sample from Glycoprotein (GP) Matrix - © Jones & Bartlett Learning, LLC one patient© using Jones transmission &electron Bartlett microscopy. Learning, LLCVP24 Nucleoprotein (NP) Serum from five patients that contained Ebola viruses gene. were grown in cell cultures and isolated for further iden NOT FOR SALE OR DISTRIBUTION tification andNOT analysis. FOR SALE OR DISTRIBUTION

The Reservoir of Ebola Viruses RNA - polymerase A retrospective study traced the Ebola virus infections to cofactor VP35 the first suspected case of the outbreak, 2-year-old Emilo Ouamiouo. The boy suffered from fever and vomiting and had black stool. The child died in Meliandou village, Gueckedou, Guinea, on December 6, 2013. A colony of thousands of Angolan free-tailed bats roosted in a hollow © Jones & Bartlett Learning,tree where Emilo and other LLC children played in Melian- ©Enve lopeJones & Bartlett Learning, LLC dou. The boy’s family hunted bats and then grilled and figure ap Matrix RNA NOT FOR SALE ORate DISTRIBUTIONthem. Past human Ebola outbreaks in other locations helical-shaped, 3-1 elongated/filamentous The structureNOT of EbolaVP40 virus.virus FOR that It is containsan enveloped,polymerase SALEssRNA (L)of OR DISTRIBUTION had been associated with outbreaks in wildlife such as negative polarity (–ssRNA). When visualized by electron duikers (small antelope), gorillas, and or microscopy, the viral particles look like thin spaghetti or long earthworms. The viral particles are 800–1,000 nm in length with a traced to hunters who butchered animals found dead uniform diameter of 80 nm. The particles can get as long as 14,000 in the rainforest. Bats are the leading suspect as the natural nm. The –ssRNA genome is encapsidated by a nucleoprotein, VP30 protein, and a viral RNA polymerase (L protein) complexed with VP35 protein to form a nucleocapsid. Embedded within the viral 850 envelope are trimeric glycoprotein spikes. The matrix proteins are involved in morphogenesis and budding/release of new infectious particles from the host cell. Teaching© Jones Tools & Bartlett Learning,9781284057898_APX3_PASS01.indd LLC 850 © Jones & Bartlett Learning, LLC LectureNOT Slides FOR in P SALEowerPoint™ OR DISTRIBUTIONFormat—The Lecture NOT FOR SALE OR DISTRIBUTION Slides provide lecture notes and images for each chapter of Understanding Viruses, Third Edition. Instruc- 21/06/16 10:18 am tors with Microsoft PowerPoint software can custom- ize the outlines, art, order of presentation, and add © Jones &their Bartlett own material. Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Instructor’s Manual —A useful guide prepared by the Author that includes Teaching Tips and other suggestions about how to approach the material in this book for your course. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Test Bank—600 items are available for testing and assessment, in additionNOT to 1,100+FOR SALE questions OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION and activities that are included in the online study and assessment tools. Web Links—Hand-selected relevant sites in virology.© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC EncountersNOT in VirologyFOR SALE—Bonus OR case DISTRIBUTION material for NOT FOR SALE OR DISTRIBUTION further application.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

xxii Preface © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 22 04/07/16 9:12 am © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORA SALEcknowledgments OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Creating a book for educational purposes involves Browning, and Bridget Yachetti, who created a set many people who labor© Jones behind &the Bartlett scenes. FirstLearning, of unique LLC and meaningful animations© Jones to visually & Bartlett Learning, LLC and foremost, I wantNOT to thank FOR the SALE editorial OR staff DISTRIBUTION explain the diverse mechanisms NOTof antiviral FOR drugs. SALE OR DISTRIBUTION at Jones & Bartlett Learning, the publisher of The book would not have been possible with- this text, who were instrumental in getting out the many individuals who were willing to sup- the first edition of the textbook off the ground: ply content for the figures. Scientific photographer Cathy Sether, Lou Bruno, Christine Myaskovsky, James Gathany went out of his way to provide Kimberly© Jones Potvin, & and Bartlett Molly Learning,Steinbach. Without LLC resource information© Jones and & images Bartlett not Learning,yet cata- LLC them,NOT there FOR would SALE not have OR been DISTRIBUTION subsequent edi- logued at the CDC’sNOT PHILFOR website. SALE UniversityOR DISTRIBUTION of tions. I had the opportunity to coauthor the third Wisconsin Oshkosh research technician Margaret edition of The Microbial Challenge. Robert I. Kras- Schuelke skillfully set up some of the virological ner’s initiative in 1980 led to the establishment assays in my research laboratory that were used as of the Division for Microbiology Undergraduate figures. Others who generously provided figures © Jones &Educators Bartlett within Learning, the American LLC Society for Micro- ©and/or Jones resources & Bartlett to create Learning, figures LLC for the text- NOT FORbiology. SALE The OR textbook-writing DISTRIBUTION experience gained NOTbook FORinclude SALE Bernard OR Moss DISTRIBUTION (Laboratory of Viral with Robert I. Krasner prepared me to put forth a Diseases, NIH), Lorena Passarelli (Kansas State greatly improved Understanding Viruses, Third Edi- University), Jennifer M. Zaspel and Gareth Powell tion manuscript. (Purdue Entomological Research Collection), The entire production team at Jones & Bartlett Gene Drecktrah (UW Oshkosh Insect Collection), Learning worked tirelessly© Jones and & with Bartlett a sense Learning, of John LLC Strous (Director of Medical© Technology, Jones & UWBartlett Learning, LLC urgency to produce NOTthe third FOR edition SALE of ORUnder DISTRIBUTION- Oshkosh), Shawn McAfee (MoraineNOT Park FOR Techni SALE- OR DISTRIBUTION standing Viruses. I am particularly grateful for Matt cal College), Howard (Beautiful Britain: Eyam Vil- Kane’s support of the revision; Audrey Schwinn’s lage and the Great Plague), Yujian Weng, Roger preparation of the manuscript for production and and Sylvia Gasser, and Renae M. Goos. Thanks assistance with the preparation of art elements to Brian Ledwell (UW Oshkosh) for his help with for the© Jonesanimations; & Bartlett and the technicalLearning, assistance LLC video capture and© Jones for incorporating & Bartlett digital Learning, tech- LLC of copyNOT editor FOR Jennifer SALE Coker, OR DISTRIBUTIONsenior production nology into theNOT classroom. FOR SALE OR DISTRIBUTION editor Nancy Hitchcock, and proofreader Christina I extend gratitude to Michael T. Osterholm, Palaia at Jones & Bartlett Learning. Professor, Environmental Health Sciences, School I extend a very heartfelt thanks to Nancy Hitch- of Public Health, and the Director of CIDRAP at cock who thoughtfully prioritized my tasks while I the University of Minnesota, for his willingness to © Jones &was Bartlett juggling Learning,the book revision LLC and teaching over ©create Jones a foreword & Bartlett for this Learning, text despite hisLLC incredible NOT FOR200 SALE students OR duringDISTRIBUTION the spring semester. Nancy NOTschedule. FOR It SALEspeaks volumesOR DISTRIBUTION for his dedication to was extremely patient with my impatience. She was virology/infectious disease education. understanding and mindful of my schedule. Produc- Peer evaluation was critical in revising and ing Understanding Viruses has been a major undertak- improving the content and accuracy of the text- ing. New content was added up to the final minutes book. Thank you for your input. I extend gratitude before being sent to the© printer. Jones The & art Bartlett package wasLearning, to the LLC following peers for their© evaluations Jones & andBartlett Learning, LLC extremely demanding.NOT Nancy FOR handled SALE the producOR DISTRIBUTION- assistance with this edition of UnderstandingNOT FOR Viruses SALE: OR DISTRIBUTION tion of the textbook with grace and her hair intact. Copy editor Jennifer Coker not only focused on the •• Prakash H. Bhuta, PhD, Eastern Washington defined duties of a copy editor, but was also a learner University of the information and raised queries that resulted in •• Brian David Byrd, PhD, MSPH, Western Car- writing© Jonesthat is clear, & Bartlett to the point, Learning, and easier LLCto read. olina University© Jones & Bartlett Learning, LLC She wasNOT indefatigable FOR SALE in her OR willingness DISTRIBUTION to review •• Julian WadeNOT Farrior, FOR PhD, SALE Gwynedd OR DISTRIBUTION Mercy new writing/content as it came in. College I am also indebted to other members of the •• Jeannette M. Loutsch, PhD, University of talented production team: Troy Liston, Jamey Science and Arts of Oklahoma O’Quinn, Joanna Lundeen, Kristin Parker, Mike •• Patricio I. Meneses, PhD Fordham University © Jones &O’Donnell, Bartlett and Learning, Marta Mitsumori. LLC I also extend © Jones•• Jessica & Parilla,Bartlett PhD, Learning, Georgia State LLC University NOT FORgratitude SALE OR for DISTRIBUTIONthe team from Fabian & Baber, NOT•• FORCarol SALEShoshkes OR Reiss,DISTRIBUTION PhD, New York including Rhonda Fabian, Jerry Baber, Stephanie University

xxiii © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

9781284057898_FMxx_00i_xxiv.indd 23 04/07/16 9:12 am •• Sarah M. Richart, PhD, Azusa Pacific University and enthusiasm of students in the classroom such as Jaime © Jones &•• BartlettPaul A. Rowley Learning,, PhD, LLCThe University of Texas at © JonesAntonio & Castillo,Bartlett Kaitlin Learning, Galow, Elainna LLC Jentz, Boda Zhao, NOT FOR SALEAustin OR DISTRIBUTION NOTYuqi FOR She, SALE Jaime ORHernandez, DISTRIBUTION Laura Jaeger, Eric Nygaard, •• Gary Stanlake, PhD, Hardin-Simmons University Travis Pire, Ashley Utech, Kristen Razner, Natalie Ray- •• Tzuen-Rong Jeremy Tzeng, PhD, Clemson mond, Devin Matznick, Heather Sharpless, Patrick Fischer, University Jeremy Kroll, Laura Hagen, Sitha Thor, Frances Delwiche, •• Xiaolu Wu, PhD, Pittsburg State University and Monica Dempsey. •• Eric Yager, PhD, Albany© Jones College & Bartlett of Pharmacy Learning, and LLCBalancing time between© Jonesresearch, & teaching,Bartlett andLearning, LLC Health Sciences NOT FOR SALE OR DISTRIBUTIONrevising this manuscript wasNOT challenging FOR SALE at times. OR DISTRIBUTION I would not have survived had it not been for lots of coffee, A very special thanks goes out to my former under- my camera, early morning walks through Menominee graduate mentor, colleague, and friend John Cronn. I Park with Roger and Sylvia Gasser, the pail full of good- appreciate his phone calls and emails to tell me about ies that often included homemade soup hung on my back recent discoveries© Jones &in BartlettScience or NatureLearning, that I mightLLC have door by Roger© Jones and Sylvia & Bartlett after a long Learning, day of teaching, LLC missedNOT and hisFOR wisdom SALE about OR teachingDISTRIBUTION and the aca- adventuresNOT with FOREric Kropp, SALE and OR Scott DISTRIBUTION McGillivray’s demic life. Other important influential mentors along FaceBook posts. Once a week, Eric and I would search the way include Bernard Moss (chief of the Laboratory for wildflowers and wildlife and visit art museums. Eric of Viral Diseases at the National Institutes of Health), tolerated my crazy schedule of getting up between mid- Bertram Jacobs, Jean M. Schmidt, Vern Winston, Gor- night and 4:00 a.m. to work on the book and he would © Jonesdon & Schrank,Bartlett and Learning, the late Denise LLC McGuire. © Jonesask me & how Bartlett the book Learning, was progressing LLC when everyone NOT FOR SALEOther colleagues OR DISTRIBUTION and instructors I would like to thank NOTelse FOR was SALE afraid ORto ask. DISTRIBUTION Lastly, I must thank Leo and for various reasons are Linda Freed, Jim Armentrout, Sasha, the cats. They made sure that I was periodically Mathew Kramer, Ethan Everett, Susan McFadden, Nancy distracted from my desk so that my blood would con- Boury, David Dilkes, Sheldon Cooper, Todd Kostman, John tinue to circulate. Koker, Chip Sitzman, Fran Widmer, and Mary Seaman, Teri Shors The textbook evolved because© Jones of the challenging& Bartlett questions Learning, LLC © JonesOshkosh, & Bartlett Wisconsin Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALEMay OR 2016 DISTRIBUTION

About the Author © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Teri Shors has been Dr. Bernard Moss in the National Institute of Allergy and NOT FOR SALE OR DISTRIBUTIONa member of the Infectious DiseasesNOT FOR at the SALE National OR Institutes DISTRIBUTION of Health, Department of Biol- Bethesda, Maryland. While her expertise centers upon ogy at the University the expression of vaccinia virus genes, she expanded of Wisconsin Osh- her research into the potential of antiviral compounds kosh since 1997; she in cranberries and other Wisconsin crops. The antiviral © Jones & Bartlett Learning, LLCwas promoted to the © Jonesresearch & Bartlettwas funded Learning, by a variety LLC of granting agencies, NOT FOR SALE OR DISTRIBUTIONrank of professor in NOTincluding FOR SALE the WiSys OR TechnologyDISTRIBUTION Foundation and a pres- 2010. Dr. Shors is a tigious Merck/AAAS award. She has mentored many stu- devoted teacher and dents engaged in independent research projects, including researcher at the pri- recent undergraduate honors theses on the Ebola outbreak marily undergraduate in West Africa and the characterization of a biofilm pres- © Joneslevel & Bartlett and has Learning,been a LLCent on an artesian well near ©Omro, Jones Wisconsin. & Bartlett Learning, LLC NOT FORrecipient SALE ofOR univer DISTRIBUTION- Her passion lies in microbiologyNOT FOR and virologySALE OReduca DISTRIBUTION- sity awards, including a distinguished teaching award, tion. In addition to authoring Understanding Viruses, Third two endowed professorships, and most recently a Dis- Edition, she authored Encounters in Virology and coau- tinguished Alumni Award from the Department of Bio- thored The Microbial Challenge, Third Edition and AIDS: logical Sciences at St. Cloud State University in 2013. The Biological Basis, Fifth Edition. She has contributed to She has© taught Jones a variety & Bartlett of courses Learning, and laboratories LLC and a variety of© other Jones texts & and Bartlett scientific Learning, papers. Initiative; LLC has madeNOT a strong FOR contributionSALE OR DISTRIBUTIONto the development of creativity; NOThumor; FOR networking; SALE OR using DISTRIBUTION current events; new courses in microbiology, virology (both classroom incorporating the latest technology in her courses; and an online courses), and molecular biology. leading collaborative, cross-disciplinary studies are the Dr. Shors’s graduate and postgraduate education is hallmarks of her talents. Dr. Shors also enjoys walking, virology based and is reflected in her research. Before photography, creating photobooks, gardening, Hallow- © Jonesteaching & Bartlett at UW Learning, Oshkosh, she LLC was a postdoctoral fellow © Joneseen, museums, & Bartlett and Learning, traveling to newLLC places. She is never NOT FORin the SALE Laboratory OR DISTRIBUTION of Viral Diseases under the direction of NOTidle FOR and SALE is a lifelong OR learner.DISTRIBUTION

xxiv Acknowledgments © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION.

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