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 infection
2021
AgBR1 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 roleSingle 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
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
Altered 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 ResearchMeSH KeywordsAedesAnimalsDisease Models, AnimalDisease VectorsFeeding BehaviorHumansMiceMosquito VectorsReceptors, InterferonSalivaZika VirusZika Virus InfectionConceptsZIKV 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
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 ResearchMeSH KeywordsAedesAnimalsDisease Models, AnimalFemaleGenitaliaHumansMaleMiceMosquito VectorsSexually Transmitted Diseases, ViralZika VirusZika Virus InfectionConceptsSexual 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 defectsFetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice
Uraki R, Jurado KA, Hwang J, Szigeti-Buck K, Horvath TL, Iwasaki A, Fikrig E. Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice. The Journal Of Infectious Diseases 2017, 215: 1720-1724. PMID: 28472297, PMCID: PMC5853330, DOI: 10.1093/infdis/jix204.Peer-Reviewed Original ResearchConceptsZika virusSexual transmissionWeight of fetusesFetal growth restrictionNaive female miceType I interferon receptorEmbryonic day 18.5Female miceGrowth restrictionMale miceOcular deformityMosquito bitesControl groupDay 18.5Fetal abnormalitiesSexual contactInterferon receptorMiceFetusesInfected malesVirusDeformityAbnormalitiesReceptorsTAM 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 concernMiceAxlReceptorsZika virus causes testicular atrophy
Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ, Hastings AK, Homer RJ, Iwasaki A, Fikrig E. Zika virus causes testicular atrophy. Science Advances 2017, 3: e1602899. PMID: 28261663, PMCID: PMC5321463, DOI: 10.1126/sciadv.1602899.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtrophyMaleMiceMice, KnockoutReceptor, Interferon alpha-betaRNA, ViralTestisTestosteroneVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusTesticular atrophyAcute viremic phaseZIKV-infected miceMosquito-borne flavivirusTestosterone-producing Leydig cellsProgressive testicular atrophyZIKV persistenceFetal infectionViremic phaseNeonatal abnormalitiesSerum testosteroneZIKV infectionNeurological dysfunctionSubcutaneous injectionZIKV replicationLeydig cellsVirus replicationVertical transmissionEpithelial cellsMiceViral RNAReproductive deficienciesAtrophyMale fertility
2016
Zika 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