2019
Aedes 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
Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
Lucas CGO, Kitoko JZ, Ferreira FM, Suzart VG, Papa MP, Coelho SVA, Cavazzoni CB, Paula-Neto HA, Olsen PC, Iwasaki A, Pereira RM, Pimentel-Coelho PM, Vale AM, de Arruda LB, Bozza MT. Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection. Nature Communications 2018, 9: 3136. PMID: 30087337, PMCID: PMC6081430, DOI: 10.1038/s41467-018-05519-4.Peer-Reviewed Original ResearchConceptsT cellsZika virusMurine adoptive transfer modelParticipation of CD4Adoptive transfer modelT cell responsesImportance of CD4Protective adaptive immunityRapid disease onsetZika virus infectionFuture vaccine designAntibody-mediated resistanceCytotoxic CD8Viral loadZIKV infectionAntibody responsePrimary infectionRecipient miceDisease onsetVirus infectionProtective effectAdaptive immunityIFNγ signalingCD4B lymphocytesTopical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner
Gopinath S, Kim MV, Rakib T, Wong PW, van Zandt M, Barry NA, Kaisho T, Goodman AL, Iwasaki A. Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner. Nature Microbiology 2018, 3: 611-621. PMID: 29632368, PMCID: PMC5918160, DOI: 10.1038/s41564-018-0138-2.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, TopicalAminoglycosidesAnimalsAnti-Bacterial AgentsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGerm-Free LifeHumansInfluenza A virusMiceMicrobiotaOligonucleotide Array Sequence AnalysisSimplexvirusToll-Like Receptor 3Transcription FactorsVirus DiseasesVirus ReplicationZika VirusConceptsToll-like receptor 3Aminoglycoside treatmentInterferon-stimulated genesViral infectionReceptor 3ISG inductionAminoglycoside antibioticsMicrobiota-independent mannerGerm-free miceAdapter-inducing interferonInterferon regulatory factor 3Herpes simplex virusTopical mucosal applicationRegulatory factor 3Dendritic cellsAntibiotic useAntiviral effectAminoglycoside applicationHost resistanceSimplex virusAntiviral resistanceVaginal mucosaMarked upregulationMucosal applicationTopical applicationType 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
Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice
Jurado KA, Yockey LJ, Wong PW, Lee S, Huttner AJ, Iwasaki A. Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nature Microbiology 2017, 3: 141-147. PMID: 29158604, PMCID: PMC5780207, DOI: 10.1038/s41564-017-0060-z.Peer-Reviewed Original ResearchConceptsCentral nervous systemZIKV infectionZika virusT cellsNeurological complicationsNervous systemBlood-brain barrier breakdownAntiviral CD8 T cellsHigh viral burdenIFNAR knockout miceCD8 T cellsEffector T cellsSusceptible mouse modelBlood-brain barrierNon-haematopoietic cellsSite of infectionIFNAR1 deficiencyViral burdenNeurological manifestationsGuillain-BarréBarrier breakdownMouse modelKnockout miceAstrocytes resultsAntiviral activityZika virus targets blood monocytes
Jurado KA, Iwasaki A. Zika virus targets blood monocytes. Nature Microbiology 2017, 2: 1460-1461. PMID: 29070824, DOI: 10.1038/s41564-017-0049-7.Peer-Reviewed Original ResearchFetal 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 ResearchConceptsZika 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
Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL, Iwasaki A. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell 2016, 166: 1247-1256.e4. PMID: 27565347, PMCID: PMC5006689, DOI: 10.1016/j.cell.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, HabitualAnimalsBrainBrain DiseasesDisease Models, AnimalFemaleFetal Growth RetardationInterferon Regulatory Factor-3MiceMice, Inbred C57BLMice, Mutant StrainsPregnancyPregnancy Complications, InfectiousReceptor, Interferon alpha-betaVaginaVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusFetal brain infectionFetal growth restrictionLocal viral replicationWild-type miceType I interferon receptorZIKV challengeTranscription factor IRF3Vaginal exposureGenital mucosaBrain infectionWT miceEarly pregnancyZIKV infectionGrowth restrictionPregnant damsVaginal infectionsZIKV replicationFetal brainMouse modelIFN pathwayVaginal tractUnborn fetusViral replicationDisease consequences