2020
CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Lin T, Geng T, Harrison AG, Yang D, Vella AT, Fikrig E, Wang P. CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses. Viruses 2020, 12: 1252. PMID: 33147869, PMCID: PMC7692144, DOI: 10.3390/v12111252.Peer-Reviewed Original ResearchConceptsChikungunya virusAlphaviral arthritisArthritogenic alphavirusesLargest immune cell populationMacrophages/T cellsImmune cell populationsInflammatory immune responseLow viral loadWild-type miceO'nyong-nyong virusWild-type animalsRheumatic manifestationsImmune infiltratesViral loadT cellsImmune responseAlphaviral diseaseArthritic diseasesTherapeutic targetCXCL10PathogenesisViral RNACell populationsArthritisFootpad
2019
AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice
Uraki R, Hastings AK, Brackney DE, Armstrong PM, Fikrig E. AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice. Npj Vaccines 2019, 4: 23. PMID: 31312526, PMCID: PMC6614468, DOI: 10.1038/s41541-019-0120-x.Peer-Reviewed Original ResearchWest Nile virus infectionWest Nile virusVirus infectionInfected Aedes aegypti mosquitoesZika virus pathogenesisMosquito salivary proteinsViral loadAedes aegypti mosquitoesLethal infectionVirus pathogenesisSevere diseaseInfectionNile virusAegypti mosquitoesMiceAntibodiesSalivary proteinsMosquitoesMeningoencephalitisPathogenesisAgBR1DiseaseLoss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia
Hastings AK, Hastings K, Uraki R, Hwang J, Gaitsch H, Dhaliwal K, Williamson E, Fikrig E. Loss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia. IScience 2019, 13: 339-350. PMID: 30884311, PMCID: PMC6424058, DOI: 10.1016/j.isci.2019.03.003.Peer-Reviewed Original ResearchZIKV infectionZIKV pathogenesisVirus infectionAxl-deficient miceZika virus pathogenesisRole of AxlZika virus infectionAlpha/beta receptorTAM receptor AxlInterferon alpha/beta receptorTAM receptorsVirus pathogenesisMouse modelEntry receptorBeta receptorsReceptor AxlViral infectionAXL inhibitorAxl receptorInfectionPathogenesisAxlMiceLess apoptosisReceptorsModeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor
Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor. Viruses 2019, 11: 35. PMID: 30625992, PMCID: PMC6356211, DOI: 10.3390/v11010035.Peer-Reviewed Original ResearchConceptsMouse modelAnimal modelsArbovirus infectionInterferon α/β receptorAlpha/beta receptorAppropriate animal modelsNatural hostInterferon alpha/beta receptorSafe therapyProtective efficacyArboviral infectionsImmune responseAdult miceBeta receptorsNew vaccinesDisease pathogenesisExtrapolation of findingsΒ receptorExperimental infectionBiosafety level 3MiceInfectionStatistical significanceVirusPathogenesis
2018
Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection
Uraki R, Hastings AK, Gloria-Soria A, Powell JR, Fikrig E. Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection. PLOS Neglected Tropical Diseases 2018, 12: e0006350. PMID: 29505571, PMCID: PMC5854422, DOI: 10.1371/journal.pntd.0006350.Peer-Reviewed Original ResearchConceptsZIKV transmissionZika virus infectionNatural transmission routeInfected miceZIKV infectionZika infectionTesting vaccinesVirus infectionIntrathoracic injectionAnimal modelsZIKVInfectionMiceTransmission routesBlood mealVector competenceVector competencyMosquitoesTransmission modelVertebrate hostsMosquito modelPathogenesisVaccine
2012
Semaphorin 7A Contributes to West Nile Virus Pathogenesis through TGF-β1/Smad6 Signaling
Sultana H, Neelakanta G, Foellmer HG, Montgomery RR, Anderson JF, Koski RA, Medzhitov RM, Fikrig E. Semaphorin 7A Contributes to West Nile Virus Pathogenesis through TGF-β1/Smad6 Signaling. The Journal Of Immunology 2012, 189: 3150-3158. PMID: 22896629, PMCID: PMC3496209, DOI: 10.4049/jimmunol.1201140.Peer-Reviewed Original ResearchConceptsRole of Sema7AWNV infectionSemaphorin 7ATGF-β1Lethal West Nile virus infectionViral pathogenesisBlood-brain barrier permeabilityWest Nile Virus PathogenesisWest Nile virus infectionMurine cortical neuronsPrimary human macrophagesViral burdenWNV pathogenesisCortical neuronsBarrier permeabilityFlaviviral infectionsVirus infectionVirus pathogenesisNervous systemImmune systemPathogenesisInfectionHuman macrophagesSema7AMice
2010
A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus
Bai F, Kong KF, Dai J, Qian F, Zhang L, Brown CR, Fikrig E, Montgometry R. A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus. The Journal Of Infectious Diseases 2010, 202: 1804-1812. PMID: 21050124, PMCID: PMC3053000, DOI: 10.1086/657416.Peer-Reviewed Original ResearchConceptsWest Nile virusPolymorphonuclear leukocytesWNV infectionNile virusHigh viremiaViral clearanceEarly deathEarly infectionControl groupProtective roleBiphasic responseInnate immunityViral pathogenesisInfectionMiceViremiaPathogenesisParadoxical roleEfficient replicationVirusCXCL1CXCL2ChemokinesCXCR2NeutrophilsFucosylation enhances colonization of ticks by Anaplasma phagocytophilum
Pedra JH, Narasimhan S, Rendić D, DePonte K, Bell‐Sakyi L, Wilson IB, Fikrig E. Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum. Cellular Microbiology 2010, 12: 1222-1234. PMID: 20331643, PMCID: PMC3250644, DOI: 10.1111/j.1462-5822.2010.01464.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilumAnaplasma phagocytophilumHuman granulocytic anaplasmosisBacterium Anaplasma phagocytophilumGranulocytic anaplasmosisPathological processesTick feedingPhagocytophilumMicrobial pathogenesisNovel mechanismPathogen colonizationTick cellsFucosylated structuresTicksPathogen invasionPathogenesis
2009
Passage through Ixodes scapularis Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of Borrelia burgdorferi
Adusumilli S, Booth CJ, Anguita J, Fikrig E. Passage through Ixodes scapularis Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of Borrelia burgdorferi. Infection And Immunity 2009, 78: 138-144. PMID: 19822652, PMCID: PMC2798202, DOI: 10.1128/iai.00470-09.Peer-Reviewed Original ResearchConceptsIxodes scapularis ticksCommon tick-borne illnessScapularis ticksTick-borne illnessB. burgdorferi sensu strictoC3H miceBurgdorferi sensu strictoLyme diseaseMiceHigh expression levelsBorrelia burgdorferiB. burgdorferiTick engorgementExpression levelsSpirochetesDiseaseArray analysisSyringe inoculationBurgdorferiPathogenic isolatesIsolatesI. scapularisArthritisVirulencePathogenesisEffective siRNA targeting of the 3′ untranslated region of the West Nile virus genome
Anthony KG, Bai F, Krishnan MN, Fikrig E, Koski RA. Effective siRNA targeting of the 3′ untranslated region of the West Nile virus genome. Antiviral Research 2009, 82: 166-168. PMID: 19135091, DOI: 10.1016/j.antiviral.2008.12.007.Peer-Reviewed Original ResearchConceptsWest Nile virusSiRNA targetsSpecific antiviral therapyRelated dengue virusAntiviral therapyWNV pathogenesisShort hairpin RNA sequencesDengue virusWNV replicationTherapeutic potentialViral replicationRNA interferenceAntiviral therapeuticsSiRNA targetingPotential antiviral therapeuticsVero cellsNile virusSequence-specific inhibitorsHuman pathogensUntranslated regionVirusVirus genomeWest Nile virus genomeTargetPathogenesis
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 virus
2007
Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis
Pal U, Wang P, Bao F, Yang X, Samanta S, Schoen R, Wormser GP, Schwartz I, Fikrig E. Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis. Journal Of Experimental Medicine 2007, 205: 133-141. PMID: 18166585, PMCID: PMC2234379, DOI: 10.1084/jem.20070962.Peer-Reviewed Original ResearchConceptsLyme arthritisMouse jointsB. burgdorferi antigensBurgdorferi-infected miceSevere arthritisSpirochete numbersArthritisHost responseLyme diseaseAffinity-purified antibodiesBorrelia burgdorferiChain reactionMiceOriginal phenotypeBasic membrane proteinMutant spirochetesGene expressionJointsInflammationPathogenesisAntigenDiseaseB. burgdorferi gene expression
2006
Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity
Li X, Liu X, Beck DS, Kantor FS, Fikrig E. Borrelia burgdorferi Lacking BBK32, a Fibronectin-Binding Protein, Retains Full Pathogenicity. Infection And Immunity 2006, 74: 3305-3313. PMID: 16714558, PMCID: PMC1479267, DOI: 10.1128/iai.02035-05.Peer-Reviewed Original ResearchConceptsB. burgdorferiFlat ticksB. burgdorferi proteinsTick biteSpirochete acquisitionLyme disease spirocheteAdverse effectsBorrelia burgdorferiFibronectin-binding proteinBurgdorferiFibronectin binding proteinMiceSpirochete life cycleLyme pathogenesisB. burgdorferi B31Mammalian hostsSyringe inoculationExpression profilesBBK32Surface lipoproteinsFibronectin bindingPathogenesisExpressionInfectionTemporal expression profiles
2004
Immunity to West Nile virus
Wang T, Fikrig E. Immunity to West Nile virus. Current Opinion In Immunology 2004, 16: 519-523. PMID: 15245749, DOI: 10.1016/j.coi.2004.05.008.Peer-Reviewed Original ResearchConceptsWN virus infectionWest Nile virusVirus infectionImportant public health concernWN virusNile virusPublic health concernActive immunizationPassive transferEffective vaccineT cellsMurine susceptibilityHealth concernExperimental modelEnvelope proteinVirusInfectionImmunityRecent studiesImmunotherapyImmunizationPathogenesisTherapyVaccine
1997
Lyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015
Fikrig E, Barthold S, Chen M, Tao H, Ali-Salaam P, Bockenstedt L, Flavell R. Lyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015. The Journal Of Infectious Diseases 1997, 175: 1000-1003. PMID: 9086169, DOI: 10.1086/513958.Peer-Reviewed Original ResearchConceptsTransgenic miceLyme borreliosisC3H/HeN miceTolerance of miceSurface protein ABorrelia burgdorferi outer surface protein ASignificant arthritisOuter surface protein ALyme arthritisProtective immunityNontransgenic littermatesHeN miceOspA antibodiesDisease pathogenesisMiceArthritisB. burgdorferi N40OspABorreliosisCellular responsesProtein AResponseImmunizationPathogenesisLittermates