2024
mosGILT controls innate immunity and germ cell development in Anopheles gambiae
Arora G, Tang X, Cui Y, Yang J, Chuang Y, Joshi J, Sajid A, Dong Y, Cresswell P, Dimopoulos G, Fikrig E. mosGILT controls innate immunity and germ cell development in Anopheles gambiae. BMC Genomics 2024, 25: 42. PMID: 38191283, PMCID: PMC10775533, DOI: 10.1186/s12864-023-09887-0.Peer-Reviewed Original ResearchConceptsGerm cell developmentAnopheles gambiaeCell developmentOvarian developmentReductase-like proteinWild-type mosquitoesPlasmodium life cycleBiological controlGrowth genesEssential regulatorRNA sequencingA. gambiaeGenesGambiaeAltered expressionImpaired ovarian developmentMosquito vectorsLife cycleMosquitoesImmune activationPlasmodium infectionTranscriptomeOogenesisRegulatorProtein
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 ResearchMeSH KeywordsAnimalsArthritisChikungunya FeverChikungunya virusImmunity, InnateMembrane ProteinsMiceMice, KnockoutViremiaConceptsVirus 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 deficiencySingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
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 regulators
2017
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells
Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm NW, Yang Y, Yu H, Li HB, Wang G, Lei X, de Zoete MR, Zhao J, Zheng Y, Chen H, Zhao Y, Jurado KA, Feng N, Shan L, Kluger Y, Lu J, Abraham C, Fikrig E, Greenberg HB, Flavell RA. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 2017, 546: 667-670. PMID: 28636595, PMCID: PMC5787375, DOI: 10.1038/nature22967.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCaspase 1DEAD-box RNA HelicasesEpithelial CellsFemaleImmunity, InnateInflammasomesInterleukin-18Intestinal MucosaIntestinesIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphate-Binding ProteinsPyroptosisReceptors, G-Protein-CoupledRNA, Double-StrandedRotavirusRotavirus Infections
2016
A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection
Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Higgs S, Vanlandingham DL, Fikrig E, Colpitts TM. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochimica Et Biophysica Acta 2016, 1860: 1898-1909. PMID: 27241849, PMCID: PMC4949077, DOI: 10.1016/j.bbagen.2016.05.033.Peer-Reviewed Original ResearchConceptsProtein degradationUbiquitin proteinGene expressionProtein expression constructsSite-directed mutagenesisViral protein degradationInnate immune signalingDengue virusProteasomal degradationProtein interactionsExpression constructsMosquito cellsSignificant human diseaseMicroarray analysisImmune signalingViral envelope proteinsVirus infectionHuman diseasesBlood feedingAmino acidsProteinMultiple functionsQRT-PCRVirion productionAntiviral function
2015
Nlrp6 regulates intestinal antiviral innate immunity
Wang P, Zhu S, Yang L, Cui S, Pan W, Jackson R, Zheng Y, Rongvaux A, Sun Q, Yang G, Gao S, Lin R, You F, Flavell R, Fikrig E. Nlrp6 regulates intestinal antiviral innate immunity. Science 2015, 350: 826-830. PMID: 26494172, PMCID: PMC4927078, DOI: 10.1126/science.aab3145.Peer-Reviewed Original ResearchConceptsI/III interferonIntestinal antiviral innate immunityEncephalomyocarditis virusEnteric virus infectionType I/III interferonsGut microbiota homeostasisAntiviral innate immunityViral RNA sensorsViral loadControl miceVirus infectionGastrointestinal tractMicrobiota homeostasisSimilar mortalityIII interferonsAntibacterial immunityInnate immunityIntestinal tractRNA helicase DHX15MiceViral RNANLRP6Murine norovirus-1RNA sensorsMortality
2014
Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes
Li MW, Wang J, Zhao YO, Fikrig E. Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes. Journal Of Biological Chemistry 2014, 289: 24885-24897. PMID: 25035430, PMCID: PMC4155657, DOI: 10.1074/jbc.m114.554519.Peer-Reviewed Original ResearchConceptsAnti-Plasmodium responseToll pathwayInnate immune responseGap junction proteinIMD pathwaySignal transductionExtracellular communicationSimultaneous knockdownAnopheles gambiaeImmune responseMidgut epitheliumInhibitor studiesKnockdownPlasmodium falciparum infectionCactusBlood mealGap junctionsVitellogenin levelsOocyst numbersAnopheles mosquitoesJunction proteinsCritical rolePathwayMRNA levelsMosquitoes
2013
UBXN1 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
The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity
Silver AC, Arjona A, Walker WE, Fikrig E. The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity. Immunity 2012, 36: 251-261. PMID: 22342842, PMCID: PMC3315694, DOI: 10.1016/j.immuni.2011.12.017.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Receptor 9Adaptive immune responsesInnate immune systemCircadian molecular clockSepsis inductionTLR9 expressionTLR9 ligandsImmune responseVaccination modelAdaptive immunityMouse modelImmune systemDisease severityHomeostatic processesCircadian rhythmBiologic processesDirect molecular linkMolecular linkRhythmSepsisImmunotherapyImmunoprophylaxisExpressionInnate
2011
Innate immune control of West Nile virus infection
Arjona A, Wang P, Montgomery RR, Fikrig E. Innate immune control of West Nile virus infection. Cellular Microbiology 2011, 13: 1648-1658. PMID: 21790942, PMCID: PMC3196381, DOI: 10.1111/j.1462-5822.2011.01649.x.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionAntiviral innate immune mechanismsLong-term neurologic sequelaeWest Nile virus infectionRe-emerging zoonotic pathogenInnate immune controlInnate immune mechanismsLife-threatening meningoencephalitisInnate immune systemNeurologic sequelaeImmune controlInflammatory mediatorsImmune mechanismsMammalian hostsVirus infectionCurrent evidenceViral infectionAntiviral effectorsImmune systemFlaviviridae familyAntiviral mechanismInfectionNile virusJAK-STAT
2010
Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I
Wang P, Arjona A, Zhang Y, Sultana H, Dai J, Yang L, LeBlanc PM, Doiron K, Saleh M, Fikrig E. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nature Immunology 2010, 11: 912-919. PMID: 20818395, PMCID: PMC3712356, DOI: 10.1038/ni.1933.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaspase 12Cells, CulturedDEAD Box Protein 58DEAD-box RNA HelicasesDNA-Binding ProteinsFibroblastsImmunity, InnateInterferon Type IMiceMice, Inbred C57BLMice, KnockoutNeuronsReceptors, VirusSignal TransductionTranscription FactorsUbiquitinationUbiquitin-Protein LigasesWest Nile FeverWest Nile virus
2009
The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus
Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus. Cell 2009, 139: 1243-1254. PMID: 20064371, PMCID: PMC2824905, DOI: 10.1016/j.cell.2009.12.017.Peer-Reviewed Original ResearchConceptsAntiviral restriction factorsWest Nile virusDengue virusInfluenza A H1N1 virusesNile virusRestriction factorsInterferon type ICellular innate immunityH1N1 virusRespiratory illnessMajor human pathogenViral infectionInnate immunityViral replicationIFITM proteinsInfluenza virusInfluenzaHost cell machineryVirusIFITMsInfectionEndosomal acidificationCellular resistanceType IHuman pathogensHuman innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfection
2008
Dysregulation 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 differences
2007
West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona A, Ledizet M, Anthony K, Bonafé N, Modis Y, Town T, Fikrig E. West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. The Journal Of Immunology 2007, 179: 8403-8409. PMID: 18056386, DOI: 10.4049/jimmunol.179.12.8403.Peer-Reviewed Original ResearchConceptsWest Nile virusInnate immune responseReceptor-interacting protein 1Immune responseMajor structural proteinVirus-associated molecular patternsDipteran cellsViral replication intermediatesRNA helicasesAdaptor molecule TRIFReplication intermediatesStructural proteinsWNV envelope proteinGlycosylation patternsMolecular patternsAntiviral stateGlycosylation profileProtein 1Murine macrophagesProinflammatory cytokinesCytokine productionImmunosuppressive effectsDsRNAImmune cellsEnvelope proteinA West Nile Virus Recombinant Protein Vaccine That Coactivates Innate and Adaptive Immunity
Huleatt J, Foellmer H, Hewitt D, Tang J, Desai P, Price A, Jacobs A, Takahashi V, Huang Y, Nakaar V, Alexopoulou L, Fikrig E, Powell T, McDonald W. A West Nile Virus Recombinant Protein Vaccine That Coactivates Innate and Adaptive Immunity. The Journal Of Infectious Diseases 2007, 195: 1607-1617. PMID: 17471430, DOI: 10.1086/517613.Peer-Reviewed Original ResearchConceptsImmune responseAntibody responseImmunoglobulin G antibody responseC3H/HeN miceWest Nile virus vaccineAdaptive immune signalsTLR5-deficient miceAntigen-specific responsesG antibody responseProtective immune responseAdaptive immune responsesToll-like receptorsWNV envelope proteinLethal WNV challengeRecombinant protein vaccineInterleukin-8 productionNeutralized viral infectivityEnzyme-linked immunosorbentEffective WNV vaccinesWNV vaccineHeN miceVirus challengeProtein vaccineVirus vaccineWNV challenge
2006
γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice
Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, Ledizet M, Koski R, Madri JA, Barrett A, Yin Z, Craft J, Fikrig E. γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice. The Journal Of Immunology 2006, 177: 1825-1832. PMID: 16849493, DOI: 10.4049/jimmunol.177.3.1825.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesGenetic Predisposition to DiseaseImmunity, CellularImmunity, InnateImmunization, SecondaryImmunoglobulin GImmunoglobulin MImmunologic MemoryLymphocyte DepletionMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaRecurrenceT-Lymphocyte SubsetsWest Nile FeverWest Nile virusConceptsGammadelta T cellsWild-type miceT cellsWN virus infectionPrimary infectionVirus infectionWN virusNaive miceSecondary challengeImmune responseAdaptive immunityCD8 memory T cellsWest Nile virus infectionMemory T cellsProtective immune responseAdaptive immune responsesAdoptive transferWest Nile virusAb responsesLethal infectionViral challengeFatal meningoencephalitisSecondary infectionInfectionMice
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
1996
Protective antibodies in murine Lyme disease arise independently of CD40 ligand.
Fikrig E, Barthold SW, Chen M, Grewal IS, Craft J, Flavell RA. Protective antibodies in murine Lyme disease arise independently of CD40 ligand. The Journal Of Immunology 1996, 157: 1-3. PMID: 8683101, DOI: 10.4049/jimmunol.157.1.1.Peer-Reviewed Original ResearchConceptsCD40L-deficient miceCD40 ligand-deficient miceMurine Lyme diseaseRegression of arthritisTransfer of serumDependent immune responsesIgG2b AbsAcute arthritisControl miceProtective antibodiesIg class switchingCD40 ligandImmune responseImmunodeficient miceLyme borreliosisLyme diseaseMiceBorrelia burgdorferiB. burgdorferiClass switchingArthritisBurgdorferiAbInfectionDisease