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 . . . . . . . . . . . . | Varicella-zoster Virus by Allison Abendroth, Paperback | Indigo Chapters