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 ResearchMeSH KeywordsAedesAnimalsCD47 AntigenFemaleHumansInsect ProteinsMosquito VectorsSalivary Proteins and PeptidesSkinZika VirusZika Virus InfectionConceptsSuppress 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 infectionmosGILT 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
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
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 diseasesDiseaseAedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination
Marin-Lopez A, Jiang J, Wang Y, Cao Y, MacNeil T, Hastings AK, Fikrig E. Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination. PLOS Neglected Tropical Diseases 2021, 15: e0009442. PMID: 34115766, PMCID: PMC8195420, DOI: 10.1371/journal.pntd.0009442.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsSuccessful viral transmissionNew mammalian hostDengue virusWild habitatsHabitat expansionGland proteinsA. aegypti vectorMammalian hostsUbiquitous expressionDENV infectionGene expressionMosquito midgutProtein componentsATPase proteinVector proteinProteinSalivary glandsBlood mealViral cycleAedes aegypti mosquitoesSusceptible hostsAedes aegyptiMosquitoesHostAgBR1 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
TRiC/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
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
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 stepHostAltered 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
2017
Zika 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 ResearchConceptsSexual 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 defects