VIRUSES This pageintentionallyleftblank VIRUSES From Understanding to Investigation S P USAN AYNE DepartmentofVeterinaryMedicineandBiomedicalSciences, TexasA&MUniversity,CollegeStation,Texas,UnitedStates AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1800,SanDiego,CA92101-4495,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyrightr2017ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicormechanical,includingphotocopying, recording,oranyinformationstorageandretrievalsystem,withoutpermissioninwritingfromthepublisher.Detailsonhowtoseek permission,furtherinformationaboutthePublisher’spermissionspoliciesandourarrangementswithorganizationssuchastheCopyright ClearanceCenterandtheCopyrightLicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions. 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BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-12-803109-4 ForInformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/books-and-journals Publisher:MicaHaley AcquisitionsEditor:LindaVersteeg-Buschman EditorialProjectManager:FentonCoulthurst ProductionProjectManager:ChrisWortley Designer:MarkRogers TypesetbyMPSLimited,Chennai,India Illustrations:IllustrationsforthisbookwereprovidedbyMarcyEdelstein, towhomthepublisherwouldliketoextendtheirthanks. Contents About the Author ix InfectionVersusDisease 55 Preface xi DevelopingModelsofVirusTransmission 56 Incubation,Latent,andInfectiousPeriods 56 Acknowledgments xiii VirusTransmission 56 1. Introduction to Animal Viruses 6. Immunity and Resistance to Viruses WhatIsaVirus? 1 InnateImmunity 62 DiversityintheWorldofViruses 2 IntrinsicImmunity 66 AreVirusesAlive? 3 SpecificImmunity 67 BasicStepsintheVirusReplication-Cycle 5 VirusesFightBack 68 GrowingViruses 5 CategorizingViruses(Taxonomy) 6 OutcomesofViralInfection 8 7. Viral Vaccines IntroductiontoViralPathogenesis 10 ClassicalversusEngineeredVaccines 73 IntroductiontoVirusTransmission 10 VaccinesProvideaSourceofAntigens 75 ReplicatingversusInactivatedVaccines 75 2. Virus Structure Killed,Inactivated,andSubunitVaccines 75 ViralVaccinesthatcontainInfectiousAgents 76 AnatomyofaVirus 13 AntigenRecognition 76 CapsidStructureandFunction 14 CorrelatesofProtection 77 CapsidsAreBuiltFromManyCopiesofOneor VaccineDevelopment 78 aFewTypesofProtein 14 AFinalWordaboutSafety 78 SimpleIcosahedralCapsids 15 LargerIcosahedralCapsids 16 ViralEnvelopes 18 8. Virus Evolution and Genetics OtherMembraneProteins 19 VirusEvolution 81 MatrixProteins 20 VirusGenetics 84 NucleocapsidStructure 21 9. Viral Pathogenesis 3. Virus Interactions With the Cell NaturalBarrierstoInfection 88 VirusInteractionswiththeCell 23 Cytoskeleton 27 PrimaryReplication 88 MovementtoSecondaryReplicationSites 88 VirusAssembly 28 GenesisofDisease 90 VirionRelease 28 VirionMaturation 29 Immunopathogenesis 91 Virulence 92 AmplificationofViralProteinsandNucleicAcids ApproachestoStudyViralPathogenesis 94 intheContextoftheInfectedCell 29 4. Methods to Study Viruses 10. Introduction to RNAViruses GrowingViruses 37 DefinitionandBasicPropertiesofRNAViruses 97 PurifyingViruses 38 SubgroupsofRNAViruses 98 VisualizingViruses 39 StructuralFeaturesofRNAVirusGenomes 100 CountingViruses 41 PrimingViralRNASynthesis 102 BasicPrinciplesofDiagnosticVirology 49 MechanismstoGenerateCappedmRNAs 102 References 52 MechanismstoGeneratePolyadenylatedmRNAs 103 MechanismstoRegulateSynthesisofGenomesand Transcripts 103 5. Virus Transmission and Epidemiology RNAVirusesandQuasispecies 103 MethodstoCountViralInfectionsandDisease 54 References 105 v vi CONTENTS 11. Family Picornaviridae 19. Family Rhabdoviridae GenomeOrganization 107 GenomeOrganization 167 VirionStructure 109 VirusStructure 167 PicornavirusReplication(PoliovirusModel) 109 OverviewofReplication 167 PicornavirusesandDisease 111 Diseases 169 12. Family Caliciviridae 20. Families Paramyxoviridae and Pneumoviridae GenomeOrganization 115 GenomeStructure/Organization 173 VirionStructure 116 VirionStructure 175 GeneralReplicationCycle 117 OverviewofReplication 176 Diseases 118 Diseases 179 13. Family Hepeviridae 21. Family Filoviridae GenomeOrganization 121 GenomeOrganization 183 VirionMorphology 121 GeneralReplicationCycleofHEV 121 VirionStructure 185 OverviewofReplication 185 Disease 123 Disease 187 14. Family Astroviridae GenomeOrganization 125 22. Family Bornaviridae VirionMorphology 125 GenomeOrganization 191 DiseasesCausedbyAstroviruses 127 VirionStructure 193 References 128 OverviewofReplication 193 Diseases 194 15. Family Flaviviridae GenomeStructure/Organization 130 23. Family Orthomyxoviridae VirionStructure 131 GenomeStructure/Organization 198 GeneralOverviewofReplication 131 VirionStructure 199 ProteinProducts 133 ClassificationandNomenclatureofOrthomyxoviruses 199 Diseases 133 OverviewofReplication 201 References 139 AntigenicDriftandAntigenicShift 205 Disease 206 16. Family Togaviridae AntiviralDrugs 207 GenomeStructure 141 Vaccines 208 VirionStructure 142 References 208 TogavirusReplication 142 Transmission 146 AlphavirusesAssociatedWithRashandArthritis 146 24. Family Bunyaviridae AlphavirusesofVeterinaryImportance 146 GenomeOrganization 209 References 148 VirionStructure 210 GeneralReplicationStrategy 211 Diseases 212 17. Family Coronaviridae CoronavirusGenomeOrganization 150 VirionStructure 152 25. Family Arenaviridae CoronavirusStructuralProteins 153 GenomeOrganization 215 CoronavirusReplicationCycle 154 VirionStructure 215 DiseasesCausedbyCoronaviruses 157 OverviewofReplication 216 References 158 DiseasesCausedbyArenaviruses 217 18. Family Arteriviridae GenomeOrganization 159 26. Family Reoviridae VirionStructure 160 GenomeOrganization 219 ReplicationCycle 160 VirusStructure 221 DiseasesCausedbyArteriviruses 160 OverviewofReplication 221 References 163 Diseases 225 vii CONTENTS 27. Family Birnaviridae 34. Family Herpesviridae GenomeStructure 227 GenomeOrganization 270 VirionStructure 227 VirusStructure 270 ReplicationCycle 228 ReplicationCycle 272 Disease 229 DiseasesCausedbyHumanHerpesviruses 273 AntiherpesviralDrugs 277 References 278 28. Introduction to DNAViruses DefinitionandBasicPropertiesofDNAViruses 231 35. Family Poxviridae ViralDNAReplication 231 GenomeOrganization 280 DNAVirusesandCellCycle 234 VirionStructure 280 Oncogenesis 236 Replication 280 Diseases 284 RabbitMyxomaVirus 285 29. Family Parvoviridae References 285 GenomeOrganization 237 VirionStructure 238 OverviewofReplication 239 36. Family Retroviridae Diseases 240 VirionStructure 289 GenomeOrganization 289 OverviewoftheRetroviralReplicationCycle 292 30. Other Small DNAViruses TheProcessofReverseTranscription 292 Integration 294 FamilyCircoviridae 243 TranscriptionofRetroviralmRNA 294 Diseases 243 StructuralProteins 295 FamilyAnelloviridae 245 Assembly,Release,andMaturation 295 References 246 MechanismsofRetroviralOncogenesis 296 31. Family Polyomaviridae 37. Replication and Pathogenesis of Human GenomeStructure 247 Immunodeficiency Virus VirionStructure 247 HistoryofHIVandAcquiredImmunodeficiency Replication 248 Syndrome 304 Transformation 250 HIVisaLentivirus 305 HumanPolyomavirusesandDisease 250 HIVProteins 307 TAT 310 REV 310 32. Family Papillomaviridae OtherHIV-1Proteins 313 GenomeStructure 253 SummaryofHIVReplication 315 VirionStructure 254 OverviewofHIVPathogenesis 317 ReplicationCycle 254 HIVTransmission 318 Disease 257 DiseaseCourse 318 AnimalPapillomaviruses 259 AntiretroviralDrugs 318 Vaccines 319 33. Family Adenoviridae 38. Family Hepadnaviridae GenomeOrganization 261 GenomeOrganization 321 VirionStructure 262 VirionStructure 323 AdenovirusReplicationCycle 263 ReplicationCycle 323 AdenovirusesandHumanDisease 265 HepatitisBVirusandDisease 326 AdenovirusesandTransformation 265 OncolyticAdenoviruses 266 AdenoviralVectors 267 Index 329 This page intentionallyleftblank About the Author Dr. Susan Payne is an associate professor in the Department of Veterinary Pathobiology at the Texas A&M University, United States. During her career, she has mentored graduate and undergraduate students at three universities and has taught virology to undergraduate,graduate, medical, and veterinary students. Those courses are the basis for this textbook. She has also had an active research career and has written over 40 peer reviewed research and review articles. She serves as an ad hoc reviewer for several virology journals. She currently lives in Caldwell, Texas with her husband, mom, five cats, one dog, nine goats, one donkey, eight chickens (if the dog has not eaten one recently), and eight guinea fowls. She is most easily available in email at [email protected]. edu. ix