2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2021
Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium
Arora G, Sajid A, Chuang YM, Dong Y, Gupta A, Gambardella K, DePonte K, Almeras L, Dimopolous G, Fikrig E. Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium. MBio 2021, 12: e03091-21. PMID: 34903042, PMCID: PMC8669493, DOI: 10.1128/mbio.03091-21.Peer-Reviewed Original ResearchConceptsLocal inflammatory responsePlasmodium berghei sporozoitesSalivary antigensInflammatory responseBerghei sporozoitesPlasmodium falciparumMosquito salivary proteinsPrevention of malariaLocal host responseAnopheline mosquitoesVertebrate hostsHost responseSaliva secretionVaccine developmentMalariaEpidemiological analysisGenerate antibodiesAntigenArthropod salivaDisease prevalenceInfectionSaliva componentsSporozoitesVector-borne diseasesDiseaseA 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
The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells
Chuang YM, Agunbiade TA, Tang XD, Freudzon M, Almeras L, Fikrig E. The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells. The Journal Of Infectious Diseases 2020, 224: 544-553. PMID: 33306099, PMCID: PMC8328219, DOI: 10.1093/infdis/jiaa759.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnophelesInsect ProteinsMalariaMicePlasmodiumProtozoan ProteinsSalivary Proteins and PeptidesSporozoitesConceptsPassive immunizationCell traversal activityMosquito saliva proteinsMosquito salivary proteinsMosquito salivaNeutrophil chemotaxisProtein monoclonal antibodyProtective effectSporozoite glidingSporozoite infectivitySporozoite traversalMonoclonal antibodiesHost skinAnopheles mosquitoesProtein 1ImmunizationBlood mealSporozoitesSalivaMiceHost cellsSaliva proteinsSalivary proteinsAntiserumVertebrate hostsTRiC/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
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 ResearchConceptsBite siteControl mosquitoesMosquito salivary proteinsInfectivity of sporozoitesMosquito salivary glandsProinflammation cytokinesSporozoite infectionRNA interference-mediated silencingPlasmodium bergheiMiceSalivary glandsSporozoitesTNFExpression of genesMosquitoesSalivary proteinsBurdenExpressionVertebrate hostsSplenocytesCytokinesInfectionCell adhesionLiverBerghei
2018
A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses
Hwang J, Jiang A, Fikrig E. A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses. Antiviral Research 2018, 161: 163-168. PMID: 30521835, PMCID: PMC6345585, DOI: 10.1016/j.antiviral.2018.11.017.Peer-Reviewed Original ResearchConceptsDengue virusSignificant morbiditySafe vaccineSynthetase inhibitionEndemic areasSynthetase inhibitorFlavivirus genusMosquito-bornePotent antagonistHost factorsGroup of pathogensVirusMultiple virusesChikungunyaHematophagous arthropod vectorsAedes sppArthropod vectorsEpidemic pathogensAdditional approachesMorbidityPathogensVaccineAntagonistMortalityHuman populationA mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission
Schleicher TR, Yang J, Freudzon M, Rembisz A, Craft S, Hamilton M, Graham M, Mlambo G, Tripathi AK, Li Y, Cresswell P, Sinnis P, Dimopoulos G, Fikrig E. A mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission. Nature Communications 2018, 9: 2908. PMID: 30046053, PMCID: PMC6060088, DOI: 10.1038/s41467-018-05374-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHost-Parasite InteractionsInsect ProteinsMalariaMosquito VectorsPlasmodiumSalivary GlandsSporozoitesConceptsSalivary gland proteinsCell traversal activityMosquito salivary gland proteinsMosquito salivaGland proteinsCell traversalInfected Anopheles mosquitoesThiol reductaseSporozoite movementVector proteinProteinPlasmodium parasitesAnopheles mosquitoesInitial infectionParasitesHost dermisVector salivaMass spectrometrySporozoitesSalivaMalariaLiverReductaseKey stepHostImmunization 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 mosquitoesMalariaAntiserumAntibodies
2016
Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLOS Neglected Tropical Diseases 2016, 10: e0004941. PMID: 27632170, PMCID: PMC5025043, DOI: 10.1371/journal.pntd.0004941.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsDengueDengue VirusFemaleHumansInsect ProteinsMiceSalivaSalivary GlandsSalivary Proteins and PeptidesU937 CellsConceptsSalivary gland extractsDengue virus infectionD7 proteinDengue virus type 1Virus type 1DENV envelope proteinAegypti salivaLymph nodesDENV infectionDENV virionsVirus infectionRelevant arbovirusesType 1InfectionHost skinBlood feedingEnvelope proteinNovel roleBinding assaysSalivaAedes aegyptiGland extractsPrimary vectorHPLC fractionsFeeding
2015
Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein
Londono-Renteria B, Troupin A, Conway MJ, Vesely D, Ledizet M, Roundy CM, Cloherty E, Jameson S, Vanlandingham D, Higgs S, Fikrig E, Colpitts TM. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein. PLOS Pathogens 2015, 11: e1005202. PMID: 26491875, PMCID: PMC4619585, DOI: 10.1371/journal.ppat.1005202.Peer-Reviewed Original ResearchConceptsDENV infectionVirus infectionDengue virusCysteine-rich venom proteinsSpecific antiviral therapyDengue virus infectionMosquito-borne flavivirusAedes aegypti cellsAntiviral therapyFlavivirus infectionMultiple flavivirusesTherapeutic measuresNew treatmentsAedes aegyptiInfectionGene targetsSerious human diseasesAegypti cellsMosquito vectorsVaccineVenom proteinsFlavivirusesHuman diseasesMosquitoesAntiserum inhibits
2014
Antivirulence Properties of an Antifreeze Protein
Heisig M, Abraham NM, Liu L, Neelakanta G, Mattessich S, Sultana H, Shang Z, Ansari JM, Killiam C, Walker W, Cooley L, Flavell RA, Agaisse H, Fikrig E. Antivirulence Properties of an Antifreeze Protein. Cell Reports 2014, 9: 417-424. PMID: 25373896, PMCID: PMC4223805, DOI: 10.1016/j.celrep.2014.09.034.Peer-Reviewed Original ResearchConceptsAntifreeze proteinsDiverse bacteriaProtein bindsWild-type animalsBiofilm formationAntivirulence agentsIAFGPMethicillin-resistant Staphylococcus aureusHost controlProteinAntifreeze glycoproteinsIxodes scapularisAntivirulence propertiesBacteriaSeptic shockTherapeutic strategiesBacterial infectionsInfectious diseasesMicrobesStaphylococcus aureusFliesBindsInfectionCatheter tubingPathogensInnexin 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
2011
Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E. Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses. PLOS Pathogens 2011, 7: e1002189. PMID: 21909258, PMCID: PMC3164632, DOI: 10.1371/journal.ppat.1002189.Peer-Reviewed Original ResearchConceptsGene expressionDiverse cellular processesPupal cuticle proteinsExpression of genesMosquito gene expressionYellow fever virusFlaviviral infectionsMosquito genesCuticle proteinsCellular processesBioinformatics analysisMosquito cellsExpression profilesMicroarray analysisDDR genesMetabolic processesHuman diseasesGenesTranscriptomic signaturesWest NileFever virusPeptidase activityWNV envelope proteinTranscriptomeAedes aegypti mosquitoesA Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
Schuijt TJ, Coumou J, Narasimhan S, Dai J, DePonte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Veer C, Hovius JW, Fikrig E. A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent. Cell Host & Microbe 2011, 10: 136-146. PMID: 21843870, PMCID: PMC3170916, DOI: 10.1016/j.chom.2011.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBorrelia burgdorferiCell Migration AssaysCloning, MolecularComplement Membrane Attack ComplexComplement Pathway, Mannose-Binding LectinFemaleGene SilencingHemolysisHumansImmunization, PassiveImmunotherapy, ActiveInsect ProteinsIxodesLarvaLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataNeutrophilsNymphPhagocytosisRabbitsRecombinant ProteinsSalivaSalivary Proteins and PeptidesSequence AlignmentConceptsComplement cascadeLyme disease agent Borrelia burgdorferiImpaired neutrophil phagocytosisTick salivary proteinsVector-borne pathogensLyme disease agentMammalian infectionVector colonizationVertebrate hostsTick midgutAlternative complement pathwayBorrelia transmissionComplement-mediated killingVector proteinNeutrophil phagocytosisEssential rolePathway inhibitorComplement pathwayDisease agentsSalivary proteinsBorrelia burgdorferiLectin inhibitorsProteinCascadeIxodes ticksAn In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection
Cheng G, Liu L, Wang P, Zhang Y, Zhao YO, Colpitts TM, Feitosa F, Anderson JF, Fikrig E. An In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection. PLOS ONE 2011, 6: e22786. PMID: 21818390, PMCID: PMC3144946, DOI: 10.1371/journal.pone.0022786.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsDengueDengue VirusEstersGene SilencingGreen Fluorescent ProteinsInsect ProteinsPlasmidsRNA, MessengerTransfectionUse 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
A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes
Cheng G, Cox J, Wang P, Krishnan MN, Dai J, Qian F, Anderson JF, Fikrig E. A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes. Cell 2010, 142: 714-725. PMID: 20797779, PMCID: PMC2954371, DOI: 10.1016/j.cell.2010.07.038.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsCulexHumansInsect ProteinsLectins, C-TypeLeukocyte Common AntigensVirus InternalizationWest Nile virusConceptsWest Nile virusWNV infectionWest Nile virus infectionArthropod-borne flavivirusBlood-feeding processVirus infectionHuman CD45Viral disseminationC-type lectinInfectionViral entryViral attachmentMosquito homologCalcium-dependent mannerNile virusMolecular understandingVivo experimentsSame pathwayNatural vectorAnaplasma 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
2007
A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Narasimhan S, Sukumaran B, Bozdogan U, Thomas V, Liang X, DePonte K, Marcantonio N, Koski RA, Anderson JF, Kantor F, Fikrig E. A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector. Cell Host & Microbe 2007, 2: 7-18. PMID: 18005713, PMCID: PMC2699493, DOI: 10.1016/j.chom.2007.06.001.Peer-Reviewed Original ResearchConceptsMammalian hostsComplex feeding sitesLyme disease agent Borrelia burgdorferiSuccessful migrationMammalian responseTick Ixodes scapularisTick salivary glandsReactive oxygen speciesFeeding sitesArthropod vectorsTick proteinsBurgdorferi-infected miceOxygen speciesEfficient vectorCritical roleSpirochete acquisitionIxodes scapularisB. burgdorferiPathogensHostBorrelia burgdorferiI. scapularisInflammatory cellsImmune cellsSurvival advantage