2024
Aedes aegypti adiponectin receptor-like protein signaling facilitates Zika virus infection
Chen T, Marín-López A, Raduwan H, Fikrig E. Aedes aegypti adiponectin receptor-like protein signaling facilitates Zika virus infection. MBio 2024, 15: e02433-24. PMID: 39373507, PMCID: PMC11559040, DOI: 10.1128/mbio.02433-24.Peer-Reviewed Original ResearchReceptor-like proteinZika virus infectionVirus infectionDevelopment of effective control strategiesSignificant public health challengeTranscriptome analysisTrypsin genesMetabolic pathwaysProtein signalingPublic health challengeViral infectionTransmission of viral diseasesAedes aegypti</i>InfectionBlood digestionZika virusProteinSignificance of signalsComplex interactionsVirusEffective control strategiesViral diseasesZikaMosquitoesPathwayZika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut
Chen T, Raduwan H, Marín-López A, Cui Y, Fikrig E. Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut. IScience 2024, 27: 110353. PMID: 39055935, PMCID: PMC11269924, DOI: 10.1016/j.isci.2024.110353.Peer-Reviewed Original ResearchAedes aegypti midgutEnteroendocrine cellsSingle-cell RNA sequencingIntestinal stem cellsVirus infectionPathogen interactionsExpressed genesRNA sequencingCopy numberTranscriptomic changesFunctional studiesInfected cellsZika virus infectionEnteroendocrineBlood digestionRNA copy numberCellular levelCell processesGenesMidgutPotential targetCell clustersCellsEnterocytesViral infection
2022
Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia
Olajiga O, Marin-Lopez A, Cardenas J, Gutierrez-Silva L, Gonzales-Pabon M, Maldonado-Ruiz L, Worges M, Fikrig E, Park Y, Londono-Renteria B. Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia. Frontiers In Epidemiology 2022, 2: 1002857. PMID: 38455331, PMCID: PMC10910902, DOI: 10.3389/fepid.2022.1002857.Peer-Reviewed Original ResearchIgG antibodiesDengue virusZika virusWest Nile virus infectionDengue disease progressionSystemic immune responsesPotential protective effectFever endemic areasDengue-endemic regionsSalivary proteinsProduction of antibodiesFemale Aedes mosquitoesSalivary gland extractsNterm-34Clinical characteristicsIgG levelsDENV infectionAntibody responseDisease progressionArboviral infectionsVirus infectionImmune responseMosquito bitesProtective effectImmunomodulatory properties
2020
A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Geng T, Lin T, Yang D, Harrison AG, Vella AT, Fikrig E, Wang P. A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus. The Journal Of Infectious Diseases 2020, 223: 2186-2196. PMID: 33161431, PMCID: PMC8205639, DOI: 10.1093/infdis/jiaa694.Peer-Reviewed Original ResearchConceptsVirus infectionSTING signalingGt miceType I IFN responseChikungunya virus infectionImmune cell infiltrationWild-type miceActivator of neutrophilsInnate immune responseExpression of interferonI IFN responseExpression of chemoattractantsRNA virus infectionDNA virus infectionInterferon genes (STING) pathwayCHIKV arthritisViremic stageArthritis progressionViral burdenArthritis pathogenesisChemokine responsesCell infiltrationJoint damageImmune responseSTING deficiencyMacrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice
Yang L, Geng T, Yang G, Ma J, Wang L, Ketkar H, Yang D, Lin T, Hwang J, Zhu S, Wang Y, Dai J, You F, Cheng G, Vella AT, Flavell RA, Fikrig E, Wang P. Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice. Communications Biology 2020, 3: 556. PMID: 33033362, PMCID: PMC7545163, DOI: 10.1038/s42003-020-01285-6.Peer-Reviewed Original ResearchConceptsMacrophage scavenger receptor 1Scavenger receptor 1Chikungunya virusReceptor 1Antiviral roleType I IFN responseChikungunya virus infectionLow-density lipoproteinImportant antiviral roleI IFN responseMarkers of autophagyCHIKV infectionViral loadArthritogenic alphavirusesVirus infectionCHIKV replicationATG5-ATG12Antiviral actionKnockout miceMSR1 expressionIFN responseInfectionMiceNsp1 proteinAutophagic functionVaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice
Wang Y, Marin-Lopez A, Jiang J, Ledizet M, Fikrig E. Vaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice. Vaccines 2020, 8: 145. PMID: 32218189, PMCID: PMC7348886, DOI: 10.3390/vaccines8020145.Peer-Reviewed Original ResearchZika virusZIKV infectionGuillain-Barre syndromeMosquito salivary proteinsZika virus infectionNeurological complicationsAcute illnessFetal microcephalyPassive immunizationActive immunizationAsymptomatic infectionInflammatory responseAedes aegypti mosquitoesVirus infectionBite siteInfectionAegypti mosquitoesImmunizationMiceSalivary proteinsAgBR1MosquitoesComplicationsHeadacheVaccination
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 proteinsMosquitoesMeningoencephalitisPathogenesisAgBR1DiseaseAedes 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 systemHIPK2 is necessary for type I interferon–mediated antiviral immunity
Cao L, Yang G, Gao S, Jing C, Montgomery RR, Yin Y, Wang P, Fikrig E, You F. HIPK2 is necessary for type I interferon–mediated antiviral immunity. Science Signaling 2019, 12 PMID: 30890658, PMCID: PMC6893850, DOI: 10.1126/scisignal.aau4604.Peer-Reviewed Original ResearchConceptsHomeodomain-interacting protein kinase 2Type I interferonProtein kinase 2I interferonRNA virus infectionAntiviral immunityN-terminal fragmentVesicular stomatitis virus infectionNuclear localizationActive caspasesKinase activityB transcriptionHIPK2 deficiencyKinase 2Virus infectionStomatitis virus infectionAntiviral responseWild-type miceVSV infectionAedes 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 proteinsVirusAntibodiesMosquitoesAntiserumLoss 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 apoptosisReceptors
2018
MiR-221 negatively regulates innate anti-viral response
Du H, Cui S, Li Y, Yang G, Wang P, Fikrig E, You F. MiR-221 negatively regulates innate anti-viral response. PLOS ONE 2018, 13: e0200385. PMID: 30089112, PMCID: PMC6082502, DOI: 10.1371/journal.pone.0200385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntagomirsDNA-Binding ProteinsDown-RegulationHEK293 CellsHerpesvirus 1, HumanHumansImmunity, InnateInterferon-betaMacrophagesMiceMice, Inbred C57BLMice, KnockoutMicroRNAsPromoter Regions, GeneticProtein Serine-Threonine KinasesRhabdoviridae InfectionsTranscription FactorsVesiculovirusConceptsAntiviral responseMiR-221Innate anti-viral responseInitial antiviral responseImmune cell activationMiR-221 expressionAnti-viral responseInnate antiviral responseInnate immune systemAnti-viral defenseIFNβ productionVirus infectionMultiple candidate targetsImmune systemCell activationCandidate targetsInfectionRNA-seq analysisCritical roleDirect bindingResponseMicroRNA regulatorsUBXN3B positively regulates STING-mediated antiviral immune responses
Yang L, Wang L, Ketkar H, Ma J, Yang G, Cui S, Geng T, Mordue DG, Fujimoto T, Cheng G, You F, Lin R, Fikrig E, Wang P. UBXN3B positively regulates STING-mediated antiviral immune responses. Nature Communications 2018, 9: 2329. PMID: 29899553, PMCID: PMC5998066, DOI: 10.1038/s41467-018-04759-8.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory X domain-containing proteinAntiviral immune responseImmune responseDeficient immune responseDomain-containing proteinsInterferon genes (STING) signalingVesicular stomatitis virus infectionDiverse biological processesStomatitis virus infectionPhosphorylation of TBK1Physiological evidenceHerpes simplex virus 1Cre-loxP approachSimplex virus 1Virus infectionAdult miceGene signalingHSV-1Biological processesPhysiological functionsVirus 1MicePrimary cellsConsequent recruitmentResponseSmall 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 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 ResearchConceptsZIKV 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
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 proliferationTAM Receptors Are Not Required for Zika Virus Infection in Mice
Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R, Gaitsch HF, Parnell LA, Cao B, Mysorekar IU, Rothlin CV, Fikrig E, Diamond MS, Iwasaki A. TAM Receptors Are Not Required for Zika Virus Infection in Mice. Cell Reports 2017, 19: 558-568. PMID: 28423319, PMCID: PMC5485843, DOI: 10.1016/j.celrep.2017.03.058.Peer-Reviewed Original ResearchConceptsTAM receptorsZika virusAbsence of IFNARGlobal public health concernNon-pregnant miceZika virus infectionAdult female micePublic health concernZIKV entryZIKV infectionFemale miceViral inoculationZIKV replicationMertk (TAM) receptorsYoung miceVirus infectionEntry receptorViral titersViral replicationCell tropismInfectionHealth concernMiceAxlReceptors
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 diseasesZika virus infection of Hofbauer cells
Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. American Journal Of Reproductive Immunology 2016, 77 PMID: 27966815, PMCID: PMC5299062, DOI: 10.1111/aji.12613.Peer-Reviewed Original ResearchConceptsCongenital Zika syndromeHofbauer cellsZika virusZIKV infectionDevelopment of CZSDengue virusSpread of ZIKVVertical transmissionFetal placental macrophagesPlacental Hofbauer cellsZika virus infectionAntenatal infectionNeonatal outcomesPlacental responsesZika syndromeVirus infectionCurrent evidenceCongenital abnormalitiesRecent studiesNeonatal developmentFetal capillariesRelated flavivirusesInfectionSpecific molecular mechanismsCertain viruses