2018
Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirus
2016
Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance
Acharya D, Wang P, Paul AM, Dai J, Gate D, Lowery JE, Stokic DS, Leis AA, Flavell RA, Town T, Fikrig E, Bai F. Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance. Journal Of Virology 2016, 91: 10.1128/jvi.01529-16. PMID: 27795421, PMCID: PMC5165211, DOI: 10.1128/jvi.01529-16.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytotoxicity, ImmunologicFemaleGene ExpressionHumansInterleukin-17MiceMice, Inbred C57BLNeuronsPrimary Cell CultureReceptors, Interleukin-17Recombinant ProteinsSurvival AnalysisT-Lymphocytes, CytotoxicTreatment OutcomeViral LoadVirus ReplicationWest Nile FeverWest Nile virusConceptsT cell cytotoxicityRecombinant IL-17AWest Nile virus infectionWNV-infected miceIL-17AT cellsViral burdenWNV infectionCell cytotoxicityInterleukin-17AVirus infectionMicrobial infectionsIL-17A-deficient miceT cell-mediated clearanceHigh viral burdenT-cell axisLethal WNV infectionSurvival of miceDay 6 postinfectionT cell functionWild-type miceDiverse immune functionsIL-17A.Proinflammatory cytokinesAutoimmune diseases
2012
IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
Wang P, Bai F, Zenewicz LA, Dai J, Gate D, Cheng G, Yang L, Qian F, Yuan X, Montgomery RR, Flavell RA, Town T, Fikrig E. IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLOS ONE 2012, 7: e44153. PMID: 22952908, PMCID: PMC3429482, DOI: 10.1371/journal.pone.0044153.Peer-Reviewed Original ResearchConceptsWild-type miceCentral nervous systemIL-22Viral loadNeutrophil migrationType miceWest Nile virus encephalitisSimilar viral loadsLethal WNV infectionIL-22 signalingHost immune responseWNV neuroinvasionVirus encephalitisCXCR2 ligandsLeukocyte infiltrateProinflammatory cytokinesChemokine receptorsImmune responseWNV infectionViral infectionNervous systemSignaling contributesExtracellular pathogensNon-redundant roleWT leukocytes
2011
prM-antibody renders immature West Nile virus infectious in vivo
Colpitts TM, Rodenhuis-Zybert I, Moesker B, Wang P, Fikrig E, Smit JM. prM-antibody renders immature West Nile virus infectious in vivo. Journal Of General Virology 2011, 92: 2281-2285. PMID: 21697345, PMCID: PMC3347797, DOI: 10.1099/vir.0.031427-0.Peer-Reviewed Original ResearchConceptsWest Nile virusInfectious West Nile virusNile virusDeath of micePrM antibodiesNeurotropic pathogensWNV particlesSevere human diseasesFamily FlaviviridaeVivo proofImmature flavivirus particlesInfectious potentialAntibodiesDiseaseViral surfaceVirus particlesPrM proteinFlavivirus particlesVirusHuman diseasesInfectionMiceFlavivirusesBrainSerum
2008
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokinesICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System
Dai J, Wang P, Bai F, Town T, Fikrig E. ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System. Journal Of Virology 2008, 82: 4164-4168. PMID: 18256150, PMCID: PMC2292986, DOI: 10.1128/jvi.02621-07.Peer-Reviewed Original ResearchConceptsWest Nile virusICAM-1Control animalsWest Nile virus neuroinvasionBlood-brain barrier leakagePathogenesis of encephalitisNile virusBlood-brain barrierLow viral loadWest Nile encephalitisCentral nervous systemICAM-1 participatesVirus neuroinvasionNeuronal damageLeukocyte infiltrationViral encephalitisViral loadBarrier leakageViral infectionNervous systemEncephalitisMiceICAMVirusAnimals
2007
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion
Arjona A, Foellmer HG, Town T, Leng L, McDonald C, Wang T, Wong SJ, Montgomery RR, Fikrig E, Bucala R. Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion. Journal Of Clinical Investigation 2007, 117: 3059-3066. PMID: 17909632, PMCID: PMC1994625, DOI: 10.1172/jci32218.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorViral neuroinvasionWest Nile virusInvolvement of MIFInhibitory factorProinflammatory cytokine macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorWNV-infected miceBlood-brain barrierLife-threatening encephalitisWild-type miceAcute WNV infectionFlavivirus West Nile virusMIF expressionMIF levelsViral loadWNV encephalitisMIF actionPharmacotherapeutic approachesInflammatory responseWNV infectionCerebrospinal fluidSusceptible individualsInnate immunity
2006
Antiviral Peptides Targeting the West Nile Virus Envelope Protein
Bai F, Town T, Pradhan D, Cox J, Ashish, Ledizet M, Anderson JF, Flavell RA, Krueger JK, Koski RA, Fikrig E. Antiviral Peptides Targeting the West Nile Virus Envelope Protein. Journal Of Virology 2006, 81: 2047-2055. PMID: 17151121, PMCID: PMC1797586, DOI: 10.1128/jvi.01840-06.Peer-Reviewed Original ResearchConceptsWest Nile virusMurine blood-brain barrierEnvelope proteinBlood-brain barrierPeptide 9West Nile encephalitisWNV envelope proteinCentral nervous systemWest Nile virus envelope proteinCDNA phage display libraryBrain parenchymaVirus envelope proteinHuman encephalitisViral envelope proteinsWNV infectionControl animalsPeptide-1Nervous systemRelated flavivirusesDengue virusAntiviral activityNew therapeuticsInhibition concentrationAntiviral peptidesNile virus
2004
Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nature Medicine 2004, 10: 1366-1373. PMID: 15558055, DOI: 10.1038/nm1140.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlood-Brain BarrierBrainEncephalitisImmunohistochemistryInflammationMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescencePermeabilityReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 3Toll-Like ReceptorsTumor Necrosis Factor-alphaViral LoadWest Nile virusConceptsToll-like receptor 3West Nile virusWNV infectionViral loadInflammatory responseReceptor 3Blood-brain barrier compromiseTLR3-deficient miceWest Nile virus entryLethal WNV infectionBlood-brain barrierWild-type miceNeuronal injuryIntracerebroventricular administrationBrain infectionCytokine productionBrain penetrationTumor necrosisTLR3 stimulationLethal encephalitisBarrier compromiseVariable severityInfectionVirus entryNile virus
2003
Borrelia burgdorferi transcriptome in the central nervous system of non-human primates
Narasimhan S, Camaino M, Liang FT, Santiago F, Laskowski M, Philipp MT, Pachner AR, Radolf JD, Fikrig E. Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 15953-15958. PMID: 14671329, PMCID: PMC307674, DOI: 10.1073/pnas.2432412100.Peer-Reviewed Original ResearchConceptsNon-human primate modelB. burgdorferiEffect of dexamethasoneCentral nervous systemHost metabolic pathwaysNon-human primatesNeurological symptomsPaucibacillary natureCNS milieuImmune statusCommon manifestationPrimate modelNervous systemExpression profilesLyme diseaseHost factorsHeart tissueGene expressionB. burgdorferi transcriptomeBorrelia burgdorferiNHPNeuroborreliosisImmunocompetentVivo gene expressionBurgdorferi