2023
Malaria: influence of Anopheles mosquito saliva on Plasmodium infection
Arora G, Chuang Y, Sinnis P, Dimopoulos G, Fikrig E. Malaria: influence of Anopheles mosquito saliva on Plasmodium infection. Trends In Immunology 2023, 44: 256-265. PMID: 36964020, PMCID: PMC10074230, DOI: 10.1016/j.it.2023.02.005.Peer-Reviewed Original ResearchConceptsAnopheles salivaPlasmodium infectionInfected female mosquitoesMosquito salivary proteinsLocal host responseComponents of salivaMosquito salivaTherapeutic strategiesHost responsePlasmodium sporozoitesVector salivaPlasmodium protozoaBlood vesselsSalivaFemale mosquitoesBlood mealAnopheline mosquitoesInfectionMalariaVector-borne diseasesSkinHost-pathogen interactionsSporozoitesSalivary proteinsMosquitoes
2021
Tick host immunity: vector immunomodulation and acquired tick resistance
Kitsou C, Fikrig E, Pal U. Tick host immunity: vector immunomodulation and acquired tick resistance. Trends In Immunology 2021, 42: 554-574. PMID: 34074602, PMCID: PMC10089699, DOI: 10.1016/j.it.2021.05.005.Peer-Reviewed Original ResearchConceptsTick-host associationsTick resistanceImmune evasion activitiesNovel preventive strategiesImmunological eventsImmunomodulatory rolePreventive strategiesTick salivaIncidental hostsNew seedsPathogen transmissionBlood mealNatural hostVector competenceNatural persistenceCritical appraisalTicksAssociationAgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection
Marin-Lopez A, Wang Y, Jiang J, Ledizet M, Fikrig E. AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection. Vaccine 2021, 39: 1675-1679. PMID: 33622591, PMCID: PMC7990057, DOI: 10.1016/j.vaccine.2021.01.072.Peer-Reviewed Original ResearchConceptsMosquito saliva proteinsPassive immunizationZIKV infectionEarly host responseDiverse clinical symptomsViral burdenSaliva proteinsClinical symptomsVaccine strategiesZika infectionHost responseModel antigenInfectionPartial protectionMiceImmunizationZIKVAntiserumIndividual antiseraAgBR1ViremiaSymptomsAntigenBloodAntibodies
2020
Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis
Černý J, Lynn G, DePonte K, Ledizet M, Narasimhan S, Fikrig E. Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis. Vaccine 2020, 38: 8121-8129. PMID: 33168347, DOI: 10.1016/j.vaccine.2020.10.087.Peer-Reviewed Original ResearchConceptsTick-borne pathogensTick immunityTick salivaTick vaccinesMultiple tick-borne pathogensIxodes scapularisGuinea pig modelTick salivary antigensTick rejectionTick Ixodes scapularisPig modelTick feedingNortheast USASalivary antigensGlobal medical problemDevelopment of vaccinesTicksMain vectorPathogensSaliva fractionsScapularisMedical problemsImmunityVaccineSalivaIxodes scapularis saliva components that elicit responses associated with acquired tick-resistance
Narasimhan S, Kurokawa C, Diktas H, Strank NO, Černý J, Murfin K, Cao Y, Lynn G, Trentleman J, Wu MJ, DePonte K, Kantor F, Anguita J, Hovius J, Fikrig E. Ixodes scapularis saliva components that elicit responses associated with acquired tick-resistance. Ticks And Tick-borne Diseases 2020, 11: 101369. PMID: 31924502, PMCID: PMC7382422, DOI: 10.1016/j.ttbdis.2019.101369.Peer-Reviewed Original ResearchConceptsTick-borne diseasesSalivary antigensAnti-tick vaccine candidatesIxodes scapularisTick salivary antigensTransmission of pathogensTick infestationTick rejectionTick proteinsViable vaccine targetsTick feedingPathogen transmissionRise worldTicksHost immune responseUrgent public health needScapularisMammalian hostsPathogensPublic health needsVaccine candidatesImmune responseSalivary glycoproteinsFeedingVaccine targeting
2019
Aedes 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 proteinsVirusAntibodiesMosquitoesAntiserum
2018
Host-specific expression of Ixodes scapularis salivary genes
Narasimhan S, Booth CJ, DePonte K, Wu MJ, Liang X, Mohanty S, Kantor F, Fikrig E. Host-specific expression of Ixodes scapularis salivary genes. Ticks And Tick-borne Diseases 2018, 10: 386-397. PMID: 30545615, DOI: 10.1016/j.ttbdis.2018.12.001.Peer-Reviewed Original ResearchConceptsVector-host interactionsTick infestationI. scapularisReservoir hostsNon-reservoir hostsHost-specific expressionRodent reservoir hostsInfected ticksPathogen transmissionZoonotic cycleSalivary genesIxodes scapularisTicksNatural hostScapularisInfestationTick biteLyme diseaseBorrelia burgdorferiLarval stagesPathogensHostPeromyscus leucopusStrong immune responseSalivary transcriptomeAltered 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
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 ResearchConceptsSalivary 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
2013
Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host
Conway MJ, Watson AM, Colpitts TM, Dragovic SM, Li Z, Wang P, Feitosa F, Shepherd DT, Ryman KD, Klimstra WB, Anderson JF, Fikrig E. Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host. Journal Of Virology 2013, 88: 164-175. PMID: 24131723, PMCID: PMC3911723, DOI: 10.1128/jvi.02235-13.Peer-Reviewed Original ResearchConceptsDengue virusDENV infectivityAedes aegypti salivaMurine lymph nodesSalivary gland extractsAegypti salivaPrevention of diseaseLymph nodesMosquito salivaDENV loadVivo modelSerine protease activityNovel targetViral attachmentViral infectivityVirus infectivitySerine protease inhibitorHeparan sulfate proteoglycanExtracellular matrix proteinsRNA knockdownProtease inhibitorsInfectivitySulfate proteoglycanCell migrationMammalian hosts
2011
A 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 ticks
2010
Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent
Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E. Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent. PLOS Pathogens 2010, 6: e1001205. PMID: 21124826, PMCID: PMC2991271, DOI: 10.1371/journal.ppat.1001205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBlotting, WesternBorrelia burgdorferiFeeding BehaviorFemaleHistamineHumansImmunizationIxodesLyme DiseaseMiceMice, Inbred C3HReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSalivaTick InfestationsTumor Protein, Translationally-Controlled 1ConceptsTick-borne pathogensB. burgdorferi transmissionTick engorgementB. burgdorferi burdenHistamine-releasing factorRapid feeding phaseBurgdorferi-infected ticksAnimal healthTick feedingTick salivaDiverse infectious agentsDisease agentsTicksIxodes scapularisLyme disease agentRNA interferenceFeeding phaseVaccine potentialQuantitative reverse transcription PCRReverse transcription-PCRHistamine releaseEffective vaccineVascular permeabilityBlood flowInfectious agents
2008
Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva
Hovius JW, Schuijt TJ, de Groot KA, Roelofs JJ, Oei GA, Marquart JA, de Beer R, Veer C, van der Poll T, Ramamoorthi N, Fikrig E, van Dam AP. Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva. The Journal Of Infectious Diseases 2008, 198: 1189-1197. PMID: 18752445, PMCID: PMC4317250, DOI: 10.1086/591917.Peer-Reviewed Original ResearchConceptsAntibody-mediated killingB. burgdorferiB. afzeliiB. gariniiEnzyme-linked immunosorbent assaySole causative agentBorrelia burgdorferi sensu latoBorrelia speciesSevere carditisOuter surface protein CImmune miceControl miceBorrelia burgdorferi sensu strictoBurgdorferi sensu latoSurface protein CSurvival advantageBurgdorferi sensu strictoSolid-phase overlayLyme borreliosisImmunosorbent assayProtein CCausative agentIxodes ticksBurgdorferiMiceSalivating for Knowledge: Potential Pharmacological Agents in Tick Saliva
Hovius JW, Levi M, Fikrig E. Salivating for Knowledge: Potential Pharmacological Agents in Tick Saliva. PLOS Medicine 2008, 5: e43. PMID: 18271624, PMCID: PMC2235897, DOI: 10.1371/journal.pmed.0050043.Peer-Reviewed Original Research
2002
A novel family of anticoagulants from the saliva of Ixodes scapularis
Narasimhan S, Koski RA, Beaulieu B, Anderson JF, Ramamoorthi N, Kantor F, Cappello M, Fikrig E. A novel family of anticoagulants from the saliva of Ixodes scapularis. Insect Molecular Biology 2002, 11: 641-650. PMID: 12421422, DOI: 10.1046/j.1365-2583.2002.00375.x.Peer-Reviewed Original ResearchConceptsN-terminal amino acid sequenceSalivary gland cDNA libraryAmino acid sequenceN-terminal sequenceCDNA libraryAcid sequenceAnticoagulant proteinsIxodes scapularisMolecular approachesTerminal sequenceIntrinsic pathwayEscherichia coliSpecific inhibitorNovel familyProteinSalp14Different functionsTick salivaSequenceBiological activityDose-dependent mannerProtease inhibitorsReversed-phase HPLCParaloguesScapularis