2021
A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice
Chuang YM, Tang XD, Fikrig E. A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice. Infection And Immunity 2021, 90: e00359-21. PMID: 34724388, PMCID: PMC8788779, DOI: 10.1128/iai.00359-21.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesFuture malaria vaccinesInfection of miceIsotype monoclonal antibodyVector antigensProtective immunityPassive immunizationMalaria vaccinePlasmodium infectionPassive transferProtein monoclonal antibodySignificant protectionSynergistic protectionMiceInfectionAntibodiesFc regionAntiserumVertebrate hostsProtein TrioImmunizationVaccineMalariaAntigenImmunity
2020
TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes
Wang Y, Uraki R, Hwang J, Fikrig E. TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes. Viruses 2020, 12: 519. PMID: 32397176, PMCID: PMC7290343, DOI: 10.3390/v12050519.Peer-Reviewed Original ResearchConceptsZika virusZIKV replicationZIKV NS1 proteinGuillain-Barré syndromeNS1 proteinTRiC/CCT complexPromising therapeutic targetZIKV infectionCongenital microcephalySpecific treatmentTherapeutic targetHost factorsVirusMosquitoesSyndromeVaccineSymptomsInfectionMicrocephalyProteinReplicationImportant role
2019
The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato
Coumou J, Wagemakers A, Narasimhan S, Schuijt TJ, Ersoz JI, Oei A, de Boer OJ, Roelofs JJTH, Fikrig E, Hovius JW. The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato. Scientific Reports 2019, 9: 1431. PMID: 30723261, PMCID: PMC6363739, DOI: 10.1038/s41598-018-37922-8.Peer-Reviewed Original ResearchConceptsMannose-Binding LectinB. burgdorferiImmune responseComplement systemRole of MBLMBL-deficient miceWhole blood stimulationIgG serum antibodiesB. burgdorferi infectionB. burgdorferi numbersHost complement systemMechanism warrants further investigationSerum-sensitive isolatesBorrelia burgdorferi sensu lato groupWarrants further investigationBorrelia burgdorferi sensu latoLater time pointsBinding lectinsSevere courseBlood stimulationDetectable antibodiesBurgdorferi sensu latoSerum antibodiesMBL deficiencyDeficient mice
2017
An essential role of PI3K in the control of West Nile virus infection
Wang L, Yang L, Fikrig E, Wang P. An essential role of PI3K in the control of West Nile virus infection. Scientific Reports 2017, 7: 3724. PMID: 28623344, PMCID: PMC5473900, DOI: 10.1038/s41598-017-03912-5.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionPI3K inhibitorsPI3KVirus infectionImmune responseK inhibitorsType I IFN responseAntiviral immune responseI IFN responseCatalytic subunit p110δTNF-α protein productionPrimary mouse macrophagesFlaviviral infectionsAntiviral immunityIFN responseViral titersClass I PI3KAntiviral roleMRNA expressionPI3K activityIFNProtein expressionInfectionMouse macrophagesCell proliferation
2013
ELF4 is critical for induction of type I interferon and the host antiviral response
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology 2013, 14: 1237-1246. PMID: 24185615, PMCID: PMC3939855, DOI: 10.1038/ni.2756.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDNA-Binding ProteinsHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmunoblottingInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSurvival AnalysisTranscription FactorsTranscriptional ActivationWest Nile FeverWest Nile virusAnopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands
Wang J, Zhang Y, Zhao YO, Li MW, Zhang L, Dragovic S, Abraham NM, Fikrig E. Anopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands. The Journal Of Infectious Diseases 2013, 208: 1161-1169. PMID: 23801601, PMCID: PMC3762383, DOI: 10.1093/infdis/jit284.Peer-Reviewed Original ResearchConceptsMosquito salivary glandsCircumsporozoite proteinSalivary glandsPlasmodium organismsPlasmodium circumsporozoite proteinMosquito-borne diseasePlasmodium life cycleSubstantial morbidityPlasmodium infectionMosquito bitesFed bloodGut wallPlasmodium sporozoitesSalivary gland proteinsPlasmodium speciesParasite loadGlandBlood mealInfectionGland proteinsVertebrate hostsVivo bioassaySporozoitesInvasionProteinUBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS
Wang P, Yang L, Cheng G, Yang G, Xu Z, You F, Sun Q, Lin R, Fikrig E, Sutton RE. UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS. Cell Reports 2013, 3: 1057-1070. PMID: 23545497, PMCID: PMC3707122, DOI: 10.1016/j.celrep.2013.02.027.Peer-Reviewed Original ResearchConceptsAntiviral immune responseInnate immune responseImmune responseLike receptorsSystemic antiviral immune responsesVirus-induced innate immune responsesDengue virus infectionType I interferon responseI interferon responseRNA virusesVirus infectionViral infectionStrong inhibitory effectViral replicationVirus replicationInterferon responseRNA virus replicationInhibitory effectWest NileMAVSVesicular stomatitisInfectionAdaptor moleculeFamily membersReceptors
2012
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection. Infection And Immunity 2012, 81: 65-79. PMID: 23071137, PMCID: PMC3536139, DOI: 10.1128/iai.00932-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsBinding SitesCell AdhesionCell Line, TumorEhrlichiaEhrlichiosisGene Expression Regulation, BacterialGlutathione TransferaseHL-60 CellsHumansMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataProtein BindingProtein Structure, TertiaryProteomeSequence Analysis, ProteinTranscription, GeneticUp-RegulationConceptsMammalian host cellsHost cellsReticulate cellsOuter membrane protein candidatesSurface proteinsOuter membrane protein AMembrane protein AA. phagocytophilum-infected ticksObligate intracellular bacteriumA. phagocytophilumGlutathione S-transferaseTranscriptional profilingSurface proteomeC-terminusAffinity purificationFamily AnaplasmataceaeProtein candidatesSelective biotinylationCellular invasionAsp14Transmission feedingAmino acidsS-transferaseIntracellular bacteriumP-selectin glycoprotein ligand-1Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2
da Silva Voorham JM, Rodenhuis-Zybert IA, Nuñez N, Colpitts TM, van der Ende-Metselaar H, Fikrig E, Diamond MS, Wilschut J, Smit JM. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2. PLOS ONE 2012, 7: e29957. PMID: 22431958, PMCID: PMC3303773, DOI: 10.1371/journal.pone.0029957.Peer-Reviewed Original ResearchConceptsAntibody-dependent enhancementImmature DENVAnti-prM antibodiesStructural proteins prMSevere dengue diseaseDengue virus antibodiesDengue virus serotype 2Dose-dependent mannerImmature particlesStandard virus preparationsVirus preparationsVirus antibodiesPrecursor membrane proteinVirus serotype 2Lethal infectionMouse modelDengue diseaseImmune serumDENV particlesProtein prMInfection studiesAntibodiesEnhanced infectivityInfectionSerotype 2
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original ResearchDengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells
Colpitts TM, Barthel S, Wang P, Fikrig E. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells. PLOS ONE 2011, 6: e24365. PMID: 21909430, PMCID: PMC3164731, DOI: 10.1371/journal.pone.0024365.Peer-Reviewed Original ResearchConceptsDENV infectionDENV CHuman liver cellsDengue virusLiver cellsDengue virus infectionTime-dependent mannerSpecific antiviralsVirus infectionInfectionAlters levelsSerious human diseasesInteresting new roleViral RNANuclear presenceMature virus particlesVirus particlesHuman diseasesFlaviviral replicationCellsCellular responsesCapsid proteinStructural proteinsVaccineUse of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector
Colpitts TM, Cox J, Nguyen A, Feitosa F, Krishnan MN, Fikrig E. Use of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector. Virology 2011, 417: 179-187. PMID: 21700306, PMCID: PMC3166580, DOI: 10.1016/j.virol.2011.06.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCadherinsCulicidaeDengue VirusInsect ProteinsInsect VectorsProtein BindingViral ProteinsWest Nile virusConceptsWest Nile virus infectionWest NileMosquito vectorsWest Nile virus envelope proteinMosquito proteinsSignificant morbidityFlavivirus infectionDengue viral proteinsVirus envelope proteinVirus infectionMosquito factorsDengue virusNovel targetInfectionMosquito cellsDengueEnvelope proteinMyosin light chain kinaseViral proteinsFlavivirusesLight chain kinasePI3-kinaseChain kinaseNS2B proteinCells
2010
Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2008
RNA interference screen for human genes associated with West Nile virus infection
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455: 242-245. PMID: 18690214, PMCID: PMC3136529, DOI: 10.1038/nature07207.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyDengue VirusEndoplasmic ReticulumGene Expression ProfilingGenome, HumanHeLa CellsHIVHumansImmunityMonocarboxylic Acid TransportersMuscle ProteinsProtein BindingRNA InterferenceUbiquitinationUbiquitin-Protein LigasesVesiculovirusVirus ReplicationWest Nile FeverWest Nile virusDysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differencesSalp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization
Hovius JW, de Jong MA, Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB. Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization. PLOS Pathogens 2008, 4: e31. PMID: 18282094, PMCID: PMC2242833, DOI: 10.1371/journal.ppat.0040031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCell Adhesion MoleculesCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugHumansIxodesLectins, C-TypeNucleosomesProtein BindingProto-Oncogene Proteins c-rafReceptors, Cell SurfaceRecombinant ProteinsRNA, MessengerSalivary Proteins and PeptidesToll-Like ReceptorsConceptsRaf-1B. burgdorferi infectionSerine/threonine kinase Raf-1Mitogen-activated protein kinase kinaseKinase Raf-1Post-transcriptional levelLyme diseaseProtein kinase kinaseRaf-1 activationBurgdorferi infectionDC-SIGNTNF-alpha mRNA stabilityHuman dendritic cell functionNucleosome remodelingTick salivary proteinsDendritic cell functionKinase kinasePro-inflammatory cytokinesAdaptive immune responsesToll-like receptorsMRNA stabilityMRNA stabilizationT cell activationMolecular mechanismsMajor vector
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 virusCutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15
Garg R, Juncadella IJ, Ramamoorthi N, Ashish, Ananthanarayanan SK, Thomas V, Rincón M, Krueger JK, Fikrig E, Yengo CM, Anguita J. Cutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15. The Journal Of Immunology 2006, 177: 6579-6583. PMID: 17082567, PMCID: PMC4302324, DOI: 10.4049/jimmunol.177.10.6579.Peer-Reviewed Original ResearchConceptsDownstream effector proteinsSrc kinase LckC-terminal residuesLipid raft reorganizationEffector proteinsKinase LckTyrosine phosphorylationMolecular basisExtracellular domainEarly stepsSalp15T cell activationSalivary proteinsCD4 coreceptorProteinCalcium fluxCell activationT cellsCellsLckRepressionPhosphorylationIL-2 productionResiduesCoreceptorCrystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes
Kanai R, Kar K, Anthony K, Gould LH, Ledizet M, Fikrig E, Marasco WA, Koski RA, Modis Y. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes. Journal Of Virology 2006, 80: 11000-11008. PMID: 16943291, PMCID: PMC1642136, DOI: 10.1128/jvi.01735-06.Peer-Reviewed Original ResearchConceptsWest Nile virus-specific antibodiesEnvelope glycoproteinTick-borne encephalitis virusWest Nile Virus Envelope GlycoproteinLife-threatening encephalitisVirus-specific antibodiesWest Nile virusMajor envelope glycoproteinAntiviral vaccinesVirus envelope glycoproteinDengue virusEncephalitis virusFlavivirus genusViral attachmentReceptor bindingWest NileTherapeutic antibodiesMolecular landscapeNile virusVirusSurface epitopesE proteinViruses e.Viral surfaceVirus surface
2005
The Lyme disease agent exploits a tick protein to infect the mammalian host
Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005, 436: 573-577. PMID: 16049492, PMCID: PMC4306560, DOI: 10.1038/nature03812.Peer-Reviewed Original Research