Current Topics in Microbiology and Immunology, Volume 342: Varicella-zoster Virus

Varicella-zoster virus is a common human pathogen that causes varicella (chickenpox), establishes latency in sensory nerve ganglia and can reactivate many years later as herpes zoster. Although the VZV genome is the smallest of the human herpesviruses, VZV genes encode at least 70 proteins. Molecular epidemiologic approaches based on genomic sequencing have documented the global distribution of VZV in distinct clades that reflect patterns of human migration. Contemporary molecular methods are making it possible to dissect how VZV gene products support the viral life cycle, including those that are necessary for viral replication, virion assembly and egress as well as those that permit take over of the host cell by modulating cell cycle regulation, survival and intrinsic antiviral responses. Progress is also being made in understanding the events in VZV pathogenesis and the viral tropisms for keratinocytes, T cells, dendritic cells and neurons during primary infection, latency and reactivation and the innate and adaptive host responses that modulate these events. New insights about molecular virology and pathogenesis have emerged from comparative studies of VZV and simian varicella virus. VZV is the only human herpesvirus for which vaccines to prevent both primary and recurrent infection are approved and VZV vaccines have had significant public health benefits. These achievements and new directions that are unfolding are described in this review of VZV basic and clinical research over many decades. Importantly, these early observationssetthestagefortheremarkableprogressthathasbeenmadeinour understandingofthemolecularbiologyofVZV, thesubtletiesofitstropismfor differentiatedhumancells, includinglymphocytesaswellasskinandneurons, and themechanismsbywhichthevirusachievesanequilibriumwiththehostsothatit persistsnotjustintheindividualbutinthehumanpopulation. v vi Preface Thepurposeofthisvolumeistoreviewkeyareasofprogressinthe?eldofVZV research, aswellasworkontherelatedSVV, writtenbythosewhohavecontributed manyofthenew?ndingsthathaveenrichedourknowledgeoftheuniquech- acteristicsofthisubiquitoushumanpathogen. AlthoughtheVZVgenomeisthe smallestamongthehumanherpesviruses, therapidlyacceleratingpaceofdiscovery about VZV and VZV host interactions re?ected in these reviews promises to continueasnewtoolsareavailableandnewhypothesesaregeneratedtoexplain howVZVhascreatedandmaintaineditsnicheinthehuman virome sos- cessfully. Further improvements in the clinical management of VZV infection shouldemergeinparallelwithbetterinsightsintoVZVmolecularvirologyand pathogenesis. Stanford, CA, June,2010 AllisonAbendroth AnnM. Arvin JenniferF. Moffat Contents TheVaricella-ZosterVirusGenome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 JeffreyI. Cohen VZVMolecularEpidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 JudithBreuer RolesofCellularTranscriptionFactorsinVZVReplication . . . . . . . . . . . . . . 43 WilliamT. Ruyechan EffectsofVaricella-ZosterVirusonCellCycleRegulatoryPathways . . . 67 JenniferF. MoffatandRebeccaJ. Greenblatt Varicella-ZosterVirusOpenReadingFrame66ProteinKinase andItsRelationshiptoAlphaherpesvirusUS3Kinases . . . . . . . . . . . . . . . . . . . . 79 AngelaErazoandPaulR. Kinchington VZVORF47SerineProteinKinaseandItsViralSubstrates . . . . . . . . . . . . . 99 TeriK. KenyonandCharlesGrose OverviewofVaricella-ZosterVirusGlycoproteinsgC, gHandgL . . . . . . 113 CharlesGrose, JohnE. Carpenter, WallenJackson, andKarenM. Duus AnalysisoftheFunctionsofGlycoproteinsEandIandTheirPromoters DuringVZVReplicationInVitroandinSkinandT-CellXenografts intheSCIDMouseModelofVZVPathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . 129 AnnM. Arvin, StefanOliver, MikeReichelt, JenniferF. Moffat, MarvinSommer, LeighZerboni, andBarbaraBerarducci Varicella-ZosterVirusGlycoproteinM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 YasukoMoriandTomohikoSadaoka vii viii Contents VaricellaZosterVirusImmuneEvasionStrategies . . . . . . . . . . . . . . . . . . . . . . . 155 AllisonAbendroth, PaulR. Kinchington, andBarrySlobedman VZVInfectionofKeratinocytes: ProductionofCell-FreeInfectious VirionsInVivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 MichaelD. GershonandAnneA. Gershon Varicella-ZosterVirusTCellTropismandthePathogenesis ofSkinInfection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 AnnM. Arvin, JenniferF. Moffat, MarvinSommer, StefanOliver, XibingChe, SusanVleck, LeighZerboni, andChia-ChiKu ExperimentalModelstoStudyVaricella-ZosterVirusInfection ofNeurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 MeganSteain, BarrySlobedman, andAllisonAbendroth MolecularCharacterizationofVaricellaZosterVirusinLatently InfectedHumanGanglia: PhysicalStateandAbundanceofVZV DNA, QuantitationofViralTranscriptsandDetection ofVZV-Speci?cProteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 YevgeniyAzarkh, DonGilden, andRandallJ. Cohrs NeurologicalDiseaseProducedbyVaricellaZosterVirusReactivation WithoutRash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 DonGilden, RandallJ. Cohrs, RaviMahalingam, andMariaA. Nagel Varicella-ZosterVirusNeurotropisminSCIDMouse Human DorsalRootGangliaXenografts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 L. Zerboni, M. Reichelt, andA. Arvin RodentModelsofVaricella-ZosterVirusNeurotropism . . . . . . . . . . . . . . . . . 277 JeffreyI. Cohen SimianVaricellaVirus: MolecularVirology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 WayneL. Gray SimianVaricellaVirusPathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 RaviMahalingam, IlhemMessaoudi, andDonGilden Varicella-ZosterVirusVaccine: MolecularGenetics . . . . . . . . . . . . . . . . . . . . . 323 D. ScottSchmid VZVTCell-MediatedImmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 AdrianaWeinbergandMyronJ. Levin Contents ix PerspectivesonVaccinesAgainstVaricella-ZosterVirusInfections . . . . 359 AnneA. GershonandMichaelD. Gershon Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 . Contributors Allison Abendroth Department of Infectious Diseases and Immunology, UniversityofSydney, BlackburnBuilding, Room601, Camperdown, NSW 2006, Australia and Centre for Virus Research, Westmead Millennium Institute, Westmead, NSW2145, Australia, allison. abendroth@sydney. edu. au AnnM. Arvin StanfordUniversitySchoolofMedicine, G3 Front Matter....Pages i-xiv The Varicella-Zoster Virus Genome....Pages 1-14 VZV Molecular Epidemiology....Pages 15-42 Roles of Cellular Transcription Factors in VZV Replication....Pages 43-65 Effects of Varicella-Zoster Virus on Cell Cycle Regulatory Pathways....Pages 67-77 Varicella-Zoster Virus Open Reading Frame 66 Protein Kinase and Its Relationship to Alphaherpesvirus US3 Kinases....Pages 79-98 VZV ORF47 Serine Protein Kinase and Its Viral Substrates....Pages 99-111 Overview of Varicella-Zoster Virus Glycoproteins gC, gH and gL....Pages 113-128 Analysis of the Functions of Glycoproteins E and I and Their Promoters During VZV Replication In Vitro and in Skin and T-Cell Xenografts in the SCID Mouse Model of VZV Pathogenesis....Pages 129-146 Varicella-Zoster Virus Glycoprotein M....Pages 147-154 Varicella Zoster Virus Immune Evasion Strategies....Pages 155-171 VZV Infection of Keratinocytes: Production of Cell-Free Infectious Virions In Vivo....Pages 173-188 Varicella-Zoster Virus T Cell Tropism and the Pathogenesis of Skin Infection....Pages 189-209 Experimental Models to Study Varicella-Zoster Virus Infection of Neurons....Pages 211-228 Molecular Characterization of Varicella Zoster Virus in Latently Infected Human Ganglia: Physical State and Abundance of VZV DNA, Quantitation of Viral Transcripts and Detection of VZV-Specific Proteins....Pages 229-241 Neurological Disease Produced by Varicella Zoster Virus Reactivation Without Rash....Pages 243-253 Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts....Pages 255-276 Rodent Models of Varicella-Zoster Virus Neurotropism....Pages 277-289 Simian Varicella Virus: Molecular Virology....Pages 291-308 Simian Varicella Virus Pathogenesis....Pages 309-321 Varicella-Zoster Virus Vaccine: Molecular Genetics....Pages 323-340 VZV T Cell-Mediated Immunity....Pages 341-357 Perspectives on Vaccines Against Varicella-Zoster Virus Infections....Pages 359-372 Back Matter....Pages 373-377 The Varicella-zoster Virus Genome -- Vzv Molecular Epidemiology -- Roles Of Cellular Transcription Factors In Vzv Replication -- Effects Of Varicella-zoster Virus On Cell Cycle Regulatory Pathways -- Varicella-zoster Virus Open Reading Frame 66 Protein Kinase And Its Relationship To Alphaherpesvirus Us3 Kinases -- Vzv Orf 47 Serine Protein Kinase And Its Viral Substrates -- Overview Of Varicella-zoster Virus Glycoproteins Gc, Gh And Gl -- Analysis Of The Function Of Glycoproteins E And I And Their Promoters During Vzv Replication In Virto And In Skin And T Cell Xenografts In The Scid Mouse Model Of Vzv Pathogenesis -- Varicella-zoster Virus Glycoprotein M -- Varicella Zoster Virus Immune Evasion Strategies -- Vzv Infection Of Keratinocytes: Production Of Cell-free Infectious Virions In Vivo -- Varicella-zoster Virus T Cell Tropism And The Pathogenesis Of Skin Infection -- Experimental Models To Study Varicella Zoster Virus Infection Of Neurons -- Molecular Characterization Of Varicella Zoster Virus (vzv) In Latently Infected Human Ganglia: Physical State And Abundance Of Vzv Dna, Quantitation Of Viral Transcripts And Detection Of Vzv-specific Proteins -- Neurological Disease Produced By Varicella Zoster Virus Reactivation Without Rash -- Varicella-zoster Virus Neurotropism In Scid Mouse-human Drg Xenografts -- Rodent Models Of Varicella-zoster Virus Neurotropism -- Simian Varicella Virus: Molecular Virology -- Simian Varicella Virus Pathogenesis -- Varicella-zoster Virus Vaccine : Molecular Genetics -- Vzv T-cell-mediated Immunity -- Perspectives On Vaccines Against Varicella-zoster Virus Infections. Allison Abendroth, Ann M. Arvin, Jennifer F. Moffat, Editors. Includes Bibliographical References And Index. This book offers a comprehensive review of basic and clinical research on Varicella-zoster Virus, the only human herpesvirus for which vaccines to prevent both primary and recurrent infection are approved.