Principles of Virology

ISBN-13: 9781683670322 / Angielski / Miękka / 2020 / 1136 str.

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

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Volume 1PrefaceAcknowledgmentsAbout the AuthorsPART I: The Science of Virology1 FoundationsLuria's CredoViruses DefinedWhy We Study VirusesViruses Are EverywhereViruses Infect All Living ThingsViruses Can Cause Human DiseaseViruses Can Be BeneficialViruses "R" UsViruses Can Cross Species BoundariesViruses Are Unique Tools To Study BiologyVirus PrehistoryViral Infections in AntiquityThe First Vaccines Microorganisms as Pathogenic AgentsDiscovery of VirusesThe Defining Properties of VirusesThe Structural Simplicity of Virus ParticlesThe Intracellular Parasitism of VirusesCataloging Animal VirusesThe Classical SystemClassification by Genome Type: the Baltimore SystemA Common Strategy for Viral PropagationPerspectivesReferencesStudy Questions2 The Infectious CycleIntroductionThe Infectious CycleThe CellEntering CellsViral RNA SynthesisViral Protein SynthesisViral Genome ReplicationAssembly of Progeny Virus ParticlesViral PathogenesisOvercoming Host DefensesCultivation of VirusesCell CultureEmbryonated EggsLaboratory AnimalsAssay of VirusesMeasurement of Infectious UnitsEfficiency of PlatingMeasurement of Virus ParticlesViral Reproduction: the Burst ConceptThe One-Step Growth CycleOne-Step Growth Analysis: a Valuable Tool for Studying Animal VirusesGlobal AnalysisDNA MicroarraysMass SpectrometryProtein-Protein InteractionsSingle-Cell VirologyPerspectivesReferencesStudy QuestionsPART II: Molecular Biology3 Genomes and GeneticsIntroductionGenome Principles and the Baltimore SystemStructure and Complexity of Viral GenomesDNA GenomesRNA GenomesWhat Do Viral Genomes Look Like?Coding StrategiesWhat Can Viral Sequences Tell Us?The "Big and Small" of Viral Genomes: Does Size Matter?The Origin of Viral GenomesGenetic Analysis of VirusesClassical Genetic MethodsEngineering Mutations into Viral GenomesEngineering Viral Genomes: Viral VectorsPerspectivesReferencesStudy Questions4 StructureIntroductionFunctions of the VirionNomenclatureMethods for Studying Virus StructureBuilding a Protective CoatHelical StructuresCapsids with Icosahedral SymmetryOther Capsid ArchitecturesPackaging the Nucleic Acid GenomeDirect Contact of the Genome with a Protein ShellPackaging by Specialized Viral ProteinsPackaging by Cellular ProteinsViruses with EnvelopesViral Envelope ComponentsSimple Enveloped Viruses: Direct Contact of External Proteins with the Capsid or NucleocapsidEnveloped Viruses with an Additional Protein LayerLarge Viruses with MultipleStructural Elements Particles with Helical or Icosahedral Parts Alternative ArchitecturesOther Components of VirionsEnzymesOther Viral ProteinsCellular MacromoleculesMechanical Properties of Virus ParticlesInvestigation of Mechanical Properties of Virus ParticlesStabilization and Destabilization of Virus ParticlesPerspectivesReferencesStudy Questions5 Attachment and EntryIntroductionAttachment of Virus Particles to CellsGeneral PrinciplesIdentification of Receptors for Virus ParticlesVirus-Receptor InteractionsEntry into CellsVirus-induced Signaling via Cell ReceptorsRoutes of entryMembrane FusionIntracellular Trafficking and UncoatingMovement of Viral and Subviral Particles within CellsUncoating of enveloped virusesUncoating of non-enveloped virusesImport of Viral Genomes into the NucleusThe Nuclear Pore ComplexNuclear Localization SignalsImport of RNA GenomesImport of DNA GenomesImport of Retroviral GenomesPerspectivesReferencesStudy Questions6 Synthesis of RNA from RNA TemplatesIntroductionThe Nature of the RNA TemplateSecondary Structures in Viral RNANaked or Nucleocapsid RNAThe RNA Synthesis MachineryIdentification of RNA-Dependent RNA PolymerasesThree-Dimensional Structures of RNA-Dependent RNA PolymerasesMechanisms of RNA SynthesisInitiationCappingElongationFunctions of Additional Polymerase DomainsRNA polymerase OligomerizationTemplate SpecificityUnwinding the RNA TemplateRole of Cellular ProteinsParadigms for Viral RNA Synthesis(+) Strand RNASynthesis of Nested Subgenomic mRNAs(.) Strand RNAAmbisense RNADouble-Stranded RNAUnique Mechanisms of mRNA and Genome Synthesis of Hepatitis Delta Satellite VirusDo Ribosomes and RNA Polymerases Collide?Origins of Diversity in RNA Virus GenomesMisincorporation of NucleotidesSegment Reassortment and RNA RecombinationRNA EditingPerspectivesReferencesStudy Questions7 Synthesis of RNA from DNA TemplatesIntroductionProperties of Cellular RNA Polymerases That Transcribe Viral DNASome Viral Genomes Must Be Converted to Templates Suitable for TranscriptionTranscription by RNA Polymerase IIRegulation of RNA Polymerase II TranscriptionCommon Properties of Proteins That Regulate TranscriptionTranscription of Viral DNA Templates by the Cellular Machinery AloneViral Proteins That Govern Transcription of DNA TemplatesPatterns of RegulationThe Human Immunodeficiency Virus Type 1 Tat Protein Autoregulates TranscriptionThe Transcriptional Cascades of DNA VirusesEntry into One of Two Alternative Transcriptional ProgramsTranscription of Viral Genes by RNA Polymerase IIIThe VA-RNA I PromoterInhibition of the Cellular Transcriptional MachineryUnusual Functions of Cellular Transcription Components in Virus-Infected CellsViral DNA-Dependent RNA PolymerasesPerspectivesReferencesStudy Questions8 ProcessingIntroductionCovalent Modification during Viral Pre-mRNA ProcessingCapping the 5' Ends of Viral mRNASynthesis of 3' Poly(A) Segments of Viral mRNAInternal Methylation of Adenosine ResiduesSplicing of Viral Pre-mRNARegulated Processing of Viral Pre-mRNAEditing of Viral mRNAsExport of RNAs from the NucleusThe Cellular Export Machinery Export of Viral mRNAPosttranscriptional Regulation of Viral or Cellular Gene Expression by Viral ProteinsTemporal Control of Viral Gene ExpressionViral Proteins Can Inhibit Cellular mRNA ProductionRegulation of Turnover of Viral and Cellular mRNAs in the CytoplasmIntrinsic TurnoverRegulation of mRNA Stability by Viral ProteinsmRNA Stabilization Can Facilitate TransformationNonsense-Mediated mRNA DecayNoncoding RNAsSmall Interfering RNAs and Micro-RNAsLong Noncoding RNAsCircular RNAsPerspectivesReferencesStudy Questions9 Replication of DNA GenomesIntroductionDNA Synthesis by the Cellular Replication MachineryEukaryotic RepliconsCellular Replication ProteinsMechanisms of Viral DNA SynthesisLessons from Simian Virus 40Replication of Other Viral DNA GenomesProperties of Viral Replication OriginsRecognition of Viral Replication OriginsViral DNA Synthesis MachinesResolution and Processing of Viral Replication ProductsExponential Accumulation of Viral GenomesViral Proteins Can Induce Synthesis of Cellular Replication ProteinsSynthesis of Viral Replication Machines and Accessory EnzymesViral DNA Replication Independent of Cellular ProteinsDelayed Synthesis of Structural Proteins Prevents Premature Packaging of DNA TemplatesInhibition of Cellular DNA SynthesisSynthesis of Viral DNA in Specialized Intracellular CompartmentsLimited Replication of Viral DNA GenomesIntegrated Parvoviral DNA Can Be Replicated as Part of the Cellular GenomeDifferent Viral Origins Regulate Replication of Epstein-Barr VirusLimited and Amplifying Replication from a Single Origin: the PapillomavirusesOrigins of Genetic Diversity in DNA VirusesFidelity of Replication by Viral DNA PolymerasesModulation of the DNA Damage ResponseRecombination of Viral GenomesPerspectivesReferencesStudy Questions10 Reverse Transcription and IntegrationRetroviral Reverse TranscriptionDiscoveryImpactThe Process of Reverse TranscriptionGeneral Properties and Structure of Retroviral Reverse TranscriptasesOther Examples of Reverse TranscriptionRetroviral DNA IntegrationThe Pathway of Integration: Integrase-Catalyzed StepsIntegrase Structure and MechanismHepadnaviral Reverse TranscriptionA DNA Virus with Reverse TranscriptaseThe Process of Hepadnaviral Reverse TranscriptionPerspectivesReferencesStudy Questions11 Protein SynthesisIntroductionMechanisms of Eukaryotic Protein SynthesisGeneral Structure of Eukaryotic mRNAThe Translation MachineryInitiationElongation and TerminationThe Diversity of Viral Translation StrategiesPolyprotein SynthesisLeaky ScanningReinitiationStopGo TranslationSuppression of TerminationRibosomal FrameshiftingBicistronic mRNAsRegulation of Translation during Viral InfectionInhibition of Translation Initiation after Viral InfectionRegulation of eIF4FRegulation of Poly(A)-Binding Protein ActivityRegulation of eIF3Interfering with RNAStress-Associated RNA GranulesPerspectivesReferencesStudy Questions12 Intracellular TraffickingIntroductionAssembly within the NucleusImport of Viral Proteins for AssemblyAssembly at the Plasma MembraneTransport of Viral Membrane Proteins to the Plasma MembraneSorting of Viral Proteins in Polarized CellsDisruption of the Secretory Pathway in Virus-Infected CellsSignal Sequence-Independent Transport of Viral Proteins to the Plasma MembraneInteractions with Internal Cellular MembranesLocalization of Viral Proteins to Compartments of the Secretory PathwayLocalization of Viral Proteins to the Nuclear MembraneTransport of Viral Genomes to Assembly SitesTransport of Genomic and Pregenomic RNA from the Nucleus to the CytoplasmTransport of Genomes from the Cytoplasm to the Plasma MembranePerspectivesReferencesStudy Questions13 Assembly, Release, and MaturationIntroductionMethods of Studying Virus Assembly and EgressStructural Studies of Virus ParticlesVisualization of Assembly and Exit by MicroscopyBiochemical and Genetic Analyses of Assembly IntermediatesMethods Based on Recombinant DNA TechnologyAssembly of Protein ShellsFormation of Structural UnitsCapsid and Nucleocapsid AssemblySelf-Assembly and Assisted Assembly ReactionsSelective Packaging of the Viral Genome and Other Components of Virus ParticlesConcerted or Sequential AssemblyRecognition and Packaging of the Nucleic Acid GenomeIncorporation of Enzymes and Other Nonstructural ProteinsAcquisition of an EnvelopeSequential Assembly of Internal Components and Budding from a Cellular MembraneCoordination of the Assembly of Internal Structures with Acquisition of the EnvelopeRelease of Virus ParticlesAssembly and Budding at the Plasma MembraneAssembly at Internal Membranes: the Problem of ExocytosisRelease of Nonenveloped Virus ParticlesMaturation of Progeny Virus ParticlesProteolytic Processing of Structural ProteinsOther Maturation ReactionsCell-to-Cell SpreadPerspectivesReferencesStudy Questions14 The Infected CellIntroductionSignal TransductionSignaling PathwaysSignaling in Virus-Infected CellsGene ExpressionInhibition of Cellular Gene ExpressionDifferential Regulation of Cellular Gene ExpressionMetabolismMethods To Study MetabolismGlucose MetabolismThe Citric Acid CycleElectron Transport and Oxidative PhosphorylationLipid MetabolismRemodeling of Cellular OrganellesThe NucleusThe CytoplasmPerspectivesReferencesStudy QuestionsAPPENDIX Structure, Genome Organization, and Infectious Cycles of Viruses Featured in this BookGlossary IndexVolume 2PrefaceAcknowledgmentsAbout the Authors1 Infections of Populations: History and EpidemiologyIntroduction to Viral PathogenesisA Brief History of Viral PathogenesisThe Relationships among Microbes and the Diseases They CauseThe First Human Viruses Identified and the Role of SerendipityNew Methods Facilitate the Study of Viruses as Causes of DiseaseViral Epidemics in HistoryEpidemics Shaped History: the 1793 Yellow Fever Epidemic in PhiladelphiaTracking Epidemics by Sequencing: West Nile Virus Spread to the Western HemisphereZoonotic Infections and Epidemics Caused by "New" VirusesThe Economic Toll of Viral Epidemics in LivestockPopulation Density and World Travel Are Accelerators of Viral TransmissionFocus on Frontline Health Care: Ebolavirus in AfricaEmergence of a Birth Defect Associated with Infection: Zika Virus in BrazilEpidemiologyFundamental ConceptsMethods Used by EpidemiologistsSurveillanceNetwork Theory and Practical ApplicationsParameters That Govern the Ability of a Virus to Infect a PopulationGeography and Population DensityClimatePerspectivesReferencesStudy Questions2 Barriers to InfectionIntroductionAn Overview of Infection and ImmunityA Game of Chess Played by MastersInitiating an InfectionSuccessful Infections Must Modulate or Bypass Host DefensesSkinRespiratory TractAlimentary TractEyesUrogenital TractPlacentaViral TropismAccessibility of Viral ReceptorsOther Host-Virus Interactions That Regulate the Infectious CycleSpread throughout the HostHematogenous SpreadNeural SpreadOrgan InvasionEntry into Organs with SinusoidsEntry into Organs That Lack SinusoidsOrgans with Dense Basement MembranesSkinShedding of Virus ParticlesRespiratory SecretionsSalivaFecesBloodUrineSemenMilkSkin LesionsTearsPerspectivesReferencesStudy Questions3 The Early Host Response: Cell Autonomous and Innate ImmunityIntroductionThe First Critical Moments: How Do Individual Cells Detect a Virus Infection?Cell Signaling Induced by Viral Entry Receptor EngagementReceptor-Mediated Recognition of Microbe-Associated Molecular PatternsCell Intrinsic DefensesApoptosis (Programmed Cell Death)Necroptosis and Other Cell Death PathwaysAutophagyEpigenetic SilencingCellular Restriction FactorsRNA InterferenceCRISPRThe Continuum Between Intrinsic and Innate ImmunitySecreted Immune Mediators of the Innate Immune ResponseOverview of Cytokine FunctionsInterferons, Cytokines of Early Warning and ActionChemokinesThe Innate Immune ResponseMonocytes/macrophagesComplementNatural Killer CellsInnate Lymphoid CellsOther Innate Immune Cells of Relevance to Viral InfectionsPerspectivesReferencesStudy Questions4 Adaptive Immunity and the Establishment of MemoryIntroductionAttributes of the Host ResponseSpeedDiversity and SpecificityMemorySelf-ControlLymphocyte Development, Diversity, and ActivationThe Hematopoietic Stem Cell LineageThe Two Arms of Adaptive ImmunityThe Major Effectors of the Adaptive Response: B and T CellsDiverse Receptors Impart Antigen Specificity to B and T CellsEvents at the Site of Infection Set the Stage for the Adaptive ResponseAcquisition of Viral Proteins by Professional Antigen-Presenting Cells Enables Production of Proinflammatory Cytokines and Establishment of InflammationActivated Antigen-Presenting Cells Leave the Site of Infection and Migrate to Lymph NodesAntigen Processing and PresentationProfessional Antigen-Presenting Cells Induce Activation via CostimulationPresentation of Antigens by Class I and Class II MHC ProteinsLymphocyte Activation Triggers Massive Cell ProliferationThe CTL (Cell-Mediated) ResponseCTLs Lyse Virus-Infected CellsControl of CTL ProliferationControl of Infection by T Cells without KillingRashes and PoxesThe Humoral (Antibody) ResponseAntibodies Are Made by Plasma CellsTypes and Functions of AntibodiesVirus Neutralization by AntibodiesAntibody-Dependent Cell-Mediated Cytotoxicity: Specific Killing by Nonspecific CellsImmunological MemoryPerspectivesReferencesStudy Questions5 Patterns and PathogenesisIntroductionAnimal Models of Human DiseasesPatterns of InfectionIncubation PeriodsMathematics of Growth Correlate with Patterns of InfectionAcute InfectionsPersistent InfectionsLatent InfectionsAbortive InfectionsTransforming InfectionsViral VirulenceMeasuring Viral VirulenceAlteration of Viral VirulenceViral Virulence GenesPathogenesisInfected Cell LysisImmunopathologyImmunosuppression Induced by Viral InfectionOncogenesisMolecular MimicryPerspectivesReferencesStudy Questions6 Cellular Transformation and OncogenesisIntroductionProperties of Transformed CellsControl of Cell ProliferationOncogenic VirusesDiscovery of Oncogenic VirusesViral Genetic Information in Transformed CellsThe Origin and Nature of Viral Transforming GenesFunctions of Viral Transforming ProteinsActivation of Cellular Signal Transduction Pathways by Viral Transforming ProteinsViral Signaling Molecules Acquired from the CellAlteration of the Production or Activity of Cellular Signal Transduction ProteinsDisruption of Cell Cycle Control Pathways by Viral Transforming ProteinsAbrogation of Restriction Point Control Exerted by the RB ProteinProduction of Virus-Specific CyclinsInactivation of Cyclin-Dependent Kinase InhibitorsTransformed Cells Increase in Size and SurviveMechanisms That Permit Survival of Transformed CellsTumorigenesis Requires Additional Changes in the Properties of Transformed CellsInhibition of Immune DefensesOther Mechanisms of Transformation and Oncogenesis by Human Tumor VirusesNontransducing Oncogenic Retroviruses: Tumorigenesis with Very Long LatencyOncogenesis by Hepatitis VirusesPerspectivesReferencesStudy Questions7 VaccinesIntroductionThe Origins of VaccinationSmallpox: a Historical PerspectiveWorldwide Vaccination Programs Can Be Dramatically EffectiveVaccine BasicsImmunization Can Be Active or PassiveActive Vaccination Strategies Stimulate Immune MemoryThe Fundamental ChallengeThe Science and Art of Making VaccinesInactivated Virus VaccinesAttenuated Virus VaccinesSubunit VaccinesVirus-Like ParticlesNucleic Acid VaccinesVaccine Technology: Delivery and Improving AntigenicityAdjuvants Stimulate an Immune ResponseDelivery and FormulationImmunotherapyThe Ongoing Quest for an AIDS VaccinePerspectivesReferencesStudy Question Puzzle8 Antiviral DrugsIntroductionA Brief History of Antiviral Drug DiscoveryDiscovering Antiviral CompoundsThe Lexicon of Antiviral DiscoveryScreening for Antiviral CompoundsComputational Approaches to Drug DiscoveryThe Difference between "R" and "D"Drug ResistanceExamples of Antiviral DrugsInhibitors of Virus Attachment and EntryInhibitors of Viral Nucleic Acid SynthesisInhibition of Viral Polyprotein Processing and AssemblyInhibition of Virus Particle ReleaseExpanding Targets for Antiviral Drug DevelopmentAttachment and Entry InhibitorsNucleic Acid-Based ApproachesProteases and Nucleic Acid Synthesis and Processing EnzymesVirus Particle AssemblyMicrobicidesTwo Stories of Antiviral SuccessCombination TherapyChallenges RemainingPerspectivesReferencesStudy Questions9 Therapeutic VirusesIntroductionPhage TherapyHistorySome Advantages and Limitations of Phage TherapyApplications in the Clinic and for Disease PreventionFuture ProspectsOncolytic Animal VirusesFrom Anecdotal Reports to Controlled Clinical TrialsRational Design of Oncolytic VirusesTwo Clinically Approved Oncolytic VirusesFuture DirectionsGene TherapyIntroductionRetroviral VectorsAdenovirus-Associated Virus VectorsFuture ProspectsVaccine VectorsDNA VirusesRNA VirusesPerspectivesReferencesStudy Questions10 Virus EvolutionVirus EvolutionHow Do Virus Populations Evolve?Two General Virus Survival Strategies Can Be DistinguishedLarge Numbers of Viral Progeny and Mutants Are Produced in Infected CellsThe Quasispecies ConceptGenetic Shift and Genetic DriftFundamental Properties of Viruses That Constrain EvolutionTwo General Pathways for Virus EvolutionEvolution of VirulenceThe Origin of VirusesWhen and How Did They Arise?Evolution of Contemporary Eukaryotic VirusesHost-Virus Relationships Drive EvolutionDNA Virus-Host RelationshipsRNA Virus-Host RelationshipsThe Host-Virus "Arms Race"Lessons from PaleovirologyEndogenous RetrovirusesDNA Fossils Derived from Other RNA Viral GenomesEndogenous Sequences from DNA VirusesShort- versus Long-Term Rates of Viral EvolutionPerspectivesReferencesStudy Questions11 EmergenceThe Spectrum of Host-Virus InteractionsStable InteractionsThe Evolving Host-Virus InteractionThe Dead-End InteractionThe Resistant HostEncountering New Hosts: Humans Constantly Provide New Venues for InfectionCommon Sources for Animal-to-Human TransmissionViral Diseases That Illustrate the Drivers of EmergencePoliomyelitis: Unexpected Consequences of Modern SanitationIntroduction of Viruses into Naïve PopulationsHantavirus Pulmonary Syndrome: Changing Animal PopulationsSevere Acute and Middle East Respiratory Syndromes (SARS and MERS): Zoonotic Coronavirus InfectionsThe Contribution to Emergence of Mutation, Recombination, or ReassortmentCanine Parvoviruses: Cat-to-Dog Host Range Switch by Two Amino Acid ChangesInfluenza Epidemics and Pandemics: Escaping the Immune Response by ReassortmentNew Technologies Uncover Previously Unrecognized VirusesHepatitis Viruses in the Human Blood SupplyA Revolution in Virus DiscoveryPerceptions and PossibilitiesVirus Names Can Be MisleadingAll Viruses Are ImportantCan We Predict the Next Viral Pandemic?Preventing Emerging Virus InfectionsPerspectivesReferencesStudy Questions12 Human Immunodeficiency Virus Type I PathogenesisIntroductionWorldwide Impact of AIDSHIV-1 Is a LentivirusDiscovery and CharacterizationDistinctive Features of the HIV-1 Reproduction Cycle and the Functions of HIV-1 ProteinsThe Viral Capsid Counters Intrinsic Defense MechanismsEntry and TransmissionEntry in the CellEntry into the BodyTransmissions in Human PopulationsThe Course of InfectionThe Acute PhaseThe Asymptomatic PhaseThe Symptomatic Phase and AIDSEffects of HIV-1 on Other Tissues and OrgansVirus ReproductionDynamics in the Absence of TreatmentDynamics of Virus Reproduction during TreatmentLatencyImmune Responses to HIV-1Innate ResponseHumoral ResponsesHIV-1 and CancerKaposi's SarcomaB-Cell LymphomasAnogenital CarcinomasProspects for Treatment and PreventionAntiviral DrugsConfronting the Problems of Persistence and LatencyGene Therapy ApproachesImmune System-Based TherapiesAntiviral Drug ProphylaxisPerspectivesReferences13 Unusual Infectious AgentsIntroductionViroidsReplicationSequence DiversityMovementPathogenesisSatellite Viruses and RNAsReplicationPathogenesisHepatitis Delta VirusPrions and Transmissible Spongiform EncephalopathiesScrapiePhysical Properties of the Scrapie AgentHuman TSEsHallmarks of TSE PathogenesisPrions and the prnp GenePrion StrainsBovine Spongiform EncephalopathyChronic Wasting DiseaseTreatment of Prion DiseasesPerspectivesReferencesStudy QuestionsAPPENDIX Epidemiology and Pathogenesis of Selected Human VirusesGlossaryIndex

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