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
Acquired tick resistance: The trail is hot
Narasimhan S, Kurokawa C, DeBlasio M, Matias J, Sajid A, Pal U, Lynn G, Fikrig E. Acquired tick resistance: The trail is hot. Parasite Immunology 2020, 43: e12808. PMID: 33187012, PMCID: PMC8058238, DOI: 10.1111/pim.12808.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsDisease Models, AnimalDisease ResistanceHost-Parasite InteractionsHumansProteomeTick InfestationsTicksCXCL10 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 populationsArthritisFootpadRepeat tick exposure elicits distinct immune responses in guinea pigs and mice
Kurokawa C, Narasimhan S, Vidyarthi A, Booth CJ, Mehta S, Meister L, Diktas H, Strank N, Lynn GE, DePonte K, Craft J, Fikrig E. Repeat tick exposure elicits distinct immune responses in guinea pigs and mice. Ticks And Tick-borne Diseases 2020, 11: 101529. PMID: 32993942, PMCID: PMC7530331, DOI: 10.1016/j.ttbdis.2020.101529.Peer-Reviewed Original ResearchConceptsGuinea pigsElicit distinct immune responsesDistinct immune responsesGuinea pig modelLocal blood flowImmune animalsInflammatory pathwaysTick rejectionMechanisms of resistanceImmune responseMouse modelVaccine candidatesBite siteBlood flowPig modelCoagulation pathwayComplement activationAcquired ResistanceProtective antigenTick detachmentTick proteinsBlood mealMiceTick infestationRNA sequencing
2019
Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice
Chuang YM, Freudzon M, Yang J, Dong Y, Dimopoulos G, Fikrig E. Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice. Infection And Immunity 2019, 87: 10.1128/iai.00326-19. PMID: 31285253, PMCID: PMC6704594, DOI: 10.1128/iai.00326-19.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnophelesCytokinesDisease Models, AnimalImmunization, PassiveInsect ProteinsMalariaMiceMice, Inbred C57BLPlasmodium bergheiConceptsBite siteControl mosquitoesMosquito salivary proteinsInfectivity of sporozoitesMosquito salivary glandsProinflammation cytokinesSporozoite infectionRNA interference-mediated silencingPlasmodium bergheiMiceSalivary glandsSporozoitesTNFExpression of genesMosquitoesSalivary proteinsBurdenExpressionVertebrate hostsSplenocytesCytokinesInfectionCell adhesionLiverBergheiAedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils
Hastings AK, Uraki R, Gaitsch H, Dhaliwal K, Stanley S, Sproch H, Williamson E, MacNeil T, Marin-Lopez A, Hwang J, Wang Y, Grover JR, Fikrig E. Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils. Journal Of Virology 2019, 93: 10.1128/jvi.00395-19. PMID: 30971475, PMCID: PMC6580965, DOI: 10.1128/jvi.00395-19.Peer-Reviewed Original ResearchConceptsVirus infectionBite siteMosquito salivaImmune cellsZika virusLocal immune environmentMosquito bite siteZika virus pathogenesisEarly viral replicationZika virus infectionFactor 1Pathogenesis of flavivirusesVirus-infected mosquitoesVirus-induced pathogenesisCXCL2 expressionImmune environmentPassive immunizationZIKV pathogenesisImmune microenvironmentAntibody responseZIKV replicationVirus pathogenesisMosquito bitesPrimary mouse neutrophilsImmune systemAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserumModeling 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
Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice
Dragovic SM, Agunbiade TA, Freudzon M, Yang J, Hastings AK, Schleicher TR, Zhou X, Craft S, Chuang YM, Gonzalez F, Li Y, Hrebikova G, Tripathi A, Mlambo G, Almeras L, Ploss A, Dimopoulos G, Fikrig E. Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice. Cell Host & Microbe 2018, 23: 523-535.e5. PMID: 29649443, PMCID: PMC5998332, DOI: 10.1016/j.chom.2018.03.008.Peer-Reviewed Original ResearchConceptsPlasmodium infectionBerghei infectionMosquito salivary gland antigensPlasmodium berghei infectionPlasmodium circumsporozoite proteinSalivary gland antigensAnopheles salivaHumanized miceActive immunizationLiver burdenVaccine candidatesInfected mosquitoesCircumsporozoite proteinHost responseMurine dermisInfectionPlasmodium falciparumMiceSalivary glandsSaliva componentsImmunizationAnopheline mosquitoesMalariaAntiserumAntibodiesSmall 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 ResearchMeSH KeywordsAnimalsBrainDisease Models, AnimalDrug CarriersMicePlacebosRabies virusRNA, Small InterferingSurvival AnalysisVirus ReplicationWest Nile FeverWest Nile virusConceptsWest 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 replicationInfectionImmunityCNSVirusAltered 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 ResearchMeSH KeywordsAedesAnimalsDisease Models, AnimalDisease VectorsFeeding BehaviorHumansMiceMosquito VectorsReceptors, InterferonSalivaZika VirusZika Virus InfectionConceptsZIKV transmissionZika virus infectionNatural transmission routeInfected miceZIKV infectionZika infectionTesting vaccinesVirus infectionIntrathoracic injectionAnimal modelsZIKVInfectionMiceTransmission routesBlood mealVector competenceVector competencyMosquitoesTransmission modelVertebrate hostsMosquito modelPathogenesisVaccineType I interferons instigate fetal demise after Zika virus infection
Yockey LJ, Jurado KA, Arora N, Millet A, Rakib T, Milano KM, Hastings AK, Fikrig E, Kong Y, Horvath TL, Weatherbee S, Kliman HJ, Coyne CB, Iwasaki A. Type I interferons instigate fetal demise after Zika virus infection. Science Immunology 2018, 3 PMID: 29305462, PMCID: PMC6049088, DOI: 10.1126/sciimmunol.aao1680.Peer-Reviewed Original ResearchConceptsZika virus infectionZIKV infectionI IFNsI interferonType I interferonGrowth restrictionFetal demiseVirus infectionSevere fetal growth restrictionType I IFNsChorionic villous explantsAdverse fetal outcomesCongenital viral infectionFetal growth restrictionMaternal-fetal barrierType IFunctional type IPlacental damageFetal outcomesPregnancy complicationsEarly pregnancyFetal resorptionZIKV diseasePregnant damsSpontaneous abortion
2017
Artificial Infection of Ticks with Borrelia burgdorferi Using a Microinjection Method and Their Detection In Vivo Using Quantitative PCR Targeting flaB RNA
Smith AA, Yang X, Fikrig E, Pal U. Artificial Infection of Ticks with Borrelia burgdorferi Using a Microinjection Method and Their Detection In Vivo Using Quantitative PCR Targeting flaB RNA. Methods In Molecular Biology 2017, 1690: 105-114. PMID: 29032540, DOI: 10.1007/978-1-4939-7383-5_9.Peer-Reviewed Original ResearchZika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses.
Hastings AK, Fikrig E. Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses. The Yale Journal Of Biology And Medicine 2017, 90: 325-330. PMID: 28656018, PMCID: PMC5482308.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsDisease Models, AnimalFemaleGenitaliaHumansMaleMiceMosquito VectorsSexually Transmitted Diseases, ViralZika VirusZika Virus InfectionConceptsSexual transmissionZika virusWorld Health OrganizationWest Nile virusAcute onset paralysisUnprotected sexual contactRoutes of transmissionNew global epidemicSevere birth defectsBody achesMild feverAnimal modelsInfected mosquitoesVaginal secretionsViral infectionMain mosquito vectorGlobal epidemicFlaviviridae familyImportant human pathogenSexual contactDisease controlHealth OrganizationZika transmissionNile virusBirth defectsFetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice
Uraki R, Jurado KA, Hwang J, Szigeti-Buck K, Horvath TL, Iwasaki A, Fikrig E. Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice. The Journal Of Infectious Diseases 2017, 215: 1720-1724. PMID: 28472297, PMCID: PMC5853330, DOI: 10.1093/infdis/jix204.Peer-Reviewed Original ResearchConceptsZika virusSexual transmissionWeight of fetusesFetal growth restrictionNaive female miceType I interferon receptorEmbryonic day 18.5Female miceGrowth restrictionMale miceOcular deformityMosquito bitesControl groupDay 18.5Fetal abnormalitiesSexual contactInterferon receptorMiceFetusesInfected malesVirusDeformityAbnormalitiesReceptorsInfection-derived lipids elicit an immune deficiency circuit in arthropods
Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JH. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nature Communications 2017, 8: 14401. PMID: 28195158, PMCID: PMC5316886, DOI: 10.1038/ncomms14401.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnaplasma marginaleAnaplasma phagocytophilumAnimalsArthropodsBorrelia burgdorferiCarrier ProteinsDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsEscherichia coliFas-Associated Death Domain ProteinGene SilencingHEK293 CellsHumansImmunologic Deficiency SyndromesIxodesLipidsLyme DiseasePhosphatidylglycerolsRecombinant ProteinsRNA, Small InterferingSignal TransductionTranscription FactorsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesX-Linked Inhibitor of Apoptosis ProteinConceptsAdaptor molecule FasImmune deficiency (IMD) pathwayPeptidoglycan recognition proteinsE3 ubiquitin ligaseLyme disease spirochete Borrelia burgdorferiIMD pathwayGram-negative bacteriaRecognition proteinsUbiquitin ligaseDeath domainApoptosis proteinDistinct bacteriaBiochemical interactionsMolecule FasSpirochete Borrelia burgdorferiReceptor networkA. marginaleProteinAnaplasma phagocytophilumBacteriaPathwayBorrelia burgdorferiInsectsLipidsArthropods
2014
A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission
Narasimhan S, Coumou J, Schuijt TJ, Boder E, Hovius JW, Fikrig E. A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission. PLOS Pathogens 2014, 10: e1004278. PMID: 25102051, PMCID: PMC4125277, DOI: 10.1371/journal.ppat.1004278.Peer-Reviewed Original Research
2012
Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection
Sukumaran B, Ogura Y, Pedra JH, Kobayashi KS, Flavell RA, Fikrig E. Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection. Pathogens And Disease 2012, 66: 211-219. PMID: 22747758, PMCID: PMC3530031, DOI: 10.1111/j.1574-695x.2012.01001.x.Peer-Reviewed Original ResearchConceptsRip2-deficient miceHuman granulocytic anaplasmosisNOD-like receptorsPhagocytophilum infectionTick-borne infectious diseaseNOD1/NOD2Obligate intracellular bacterium Anaplasma phagocytophilumInflammatory protein-2Host immune responseInnate immune pathwaysProtein 2Anaplasma phagocytophilum infectionHuman primary neutrophilsBacterium Anaplasma phagocytophilumHigh bacterial loadWild-type controlsImmune controlIL-12Immune clearanceImmune responseImmune pathwaysHost responseKC responsesHost defenseInfectious diseasesSemaphorin 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
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