2023
Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpression
2022
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionImpact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines
Yang Y, Iwasaki A. Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines. Current HIV/AIDS Reports 2021, 19: 5-16. PMID: 34843064, PMCID: PMC8628277, DOI: 10.1007/s11904-021-00590-x.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human immune deficiency virus (HIV) infectionSARS-CoV-2 acute infectionImmune systemSevere acute respiratory syndrome coronavirus 2Severe SARS-CoV-2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Chronic HIV infectionSyndrome coronavirus 2Effectiveness of vaccinesHost immune systemCOVID-19 diseaseRecent FindingsPeopleAntiretroviral therapyImmunological changesAcute infectionHIV infectionDisease complicationsPersistent inflammationCoronavirus 2Functional impairmentVirus infectionImmune response
2020
Commensal Microbiota Modulation of Natural Resistance to Virus Infection
Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal Microbiota Modulation of Natural Resistance to Virus Infection. Cell 2020, 183: 1312-1324.e10. PMID: 33212011, PMCID: PMC7799371, DOI: 10.1016/j.cell.2020.10.047.Peer-Reviewed Original ResearchConceptsMicrobial moleculesVesicular stomatitis virusCommensal microbesSpecific commensal microbesInduction of IFNVirus infectionNatural resistanceOuter membraneGut commensal microbesIFN-β expressionImmune system regulationHuman diseasesPhysiological importanceInduces expressionSource of IFNMicrobesHomeostatic conditionsStomatitis virusIFN-IsMicrobiota modulationAntiviral immunityCrucial mediatorIFNPolysaccharide AAntiviral activity
2019
Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietIAV infectionT cellsGlobal health care concernHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionHealth care concernHigh-carbohydrate dietInfluenza diseaseKD feedingVirus infectionNew therapiesAntiviral resistanceHepatic ketogenesisCare concernsCell responsesInfectionBarrier functionDietMetabolic adaptationMurine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice
Pi R, Iwasaki A, Sewald X, Mothes W, Uchil PD. Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00930-19. PMID: 31434732, PMCID: PMC6803250, DOI: 10.1128/jvi.00930-19.Peer-Reviewed Original ResearchConceptsPopliteal lymph nodesFriend murine leukemia virusInnate immune sensing pathwaysToll-like receptor 7Viral spreadMurine leukemia virusCell-deficient miceType I interferon responseWild-type miceCell populationsType I interferonLeukemia virusRobust virus replicationI interferon responseAntiviral intervention strategiesInfected cell typesSentinel macrophagesAdoptive transferCell typesLymph nodesReceptor 7Virus infectionInnate sensingB cellsI interferonLow ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virusKetogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg E, Molony R, Sidorov S, Kudo E, Dixit V, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. The Journal Of Immunology 2019, 202: 62.7-62.7. DOI: 10.4049/jimmunol.202.supp.62.7.Peer-Reviewed Original ResearchΓδ T cellsKetogenic dietIAV infectionT cellsHigh-fat high-carbohydrate dietHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionAnti-viral resistanceHigh-carbohydrate dietInfluenza diseaseKD feedingNovel therapiesVirus infectionGlobal healthcare concernHepatic ketogenesisAbstract InfluenzaCell responsesHealthcare concernInfectionBarrier functionDietAedes 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 lymphocytesType 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
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonOlder adultsIFN inductionRetinoic acid-inducible gene IAcid-inducible gene IHealthy human donorsType I interferonRespiratory influenzaProinflammatory cytokinesVirus infectionType I IFN genesAdult monocytesAntiviral resistanceTranscription factor IRF8IFN responseHuman donorsMonocytesIncreased proteasomal degradationHuman monocytesYoung adultsIRF8 expressionIAV RNAInfected cellsZika 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 ResearchTAM 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 concernMiceAxlReceptors
2016
Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature 2016, 533: 552-556. PMID: 27225131, PMCID: PMC4883597, DOI: 10.1038/nature17979.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralBiological TransportBlood-Brain BarrierB-LymphocytesCapillary PermeabilityCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGanglia, SpinalHerpes GenitalisHerpesvirus 2, HumanHistocompatibility Antigens Class IImmunologic MemoryIntegrin alpha4Interferon-gammaMiceNerve TissueNervous SystemNeuronsNoseReceptors, FcSpinal CordVesiculovirus
2014
Innate immunity to influenza virus infection
Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nature Reviews Immunology 2014, 14: 315-328. PMID: 24762827, PMCID: PMC4104278, DOI: 10.1038/nri3665.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionToll-like receptor 7T cell responsesVirus infectionInterferon-stimulated genesIL-1βNLRP3 inflammasomeViral challengeB cellsCell responsesHigh-dose viral challengeInfluenza virusAntiviral B cellsMultiple pattern recognition receptorsPlasmacytoid dendritic cellsAdaptive immune responsesInfected cellsRetinoic acid-inducible gene IAirway epithelial cellsAcid-inducible gene IPattern recognition receptorsInfluenza virus-infected cellsVirus-infected cellsAntiviral defense genesDendritic cells
2013
Generating protective immunity against genital herpes
Shin H, Iwasaki A. Generating protective immunity against genital herpes. Trends In Immunology 2013, 34: 487-494. PMID: 24012144, PMCID: PMC3819030, DOI: 10.1016/j.it.2013.08.001.Peer-Reviewed Original ResearchConceptsGenital herpesHerpes simplex virus infectionSimplex virus infectionSignificant risk factorsClinical vaccine trialsRecurrent symptomsHSV infectionProtective immunityViral sheddingVaccine trialsRisk factorsChronic diseasesVirus infectionHIV-1Clear infectionAntiviral drugsHost responseHerpesVaccine designInfectionMillions of peopleSpread of diseaseDiseaseRecent studiesVaccineInnate immunity
Iwasaki A, Peiris M. Innate immunity. 2013, 267-282. DOI: 10.1002/9781118636817.ch17.Peer-Reviewed Original ResearchToll-like receptorsNOD-like receptorsImmune responseVirus infectionInfluenza virusHundreds of IFNProtective host responseInfluenza virus infectionAdaptive immune responsesInnate immune responseType I IFNInfluenza virus replicationInnate immune systemDendritic cellsNK cellsInfluenza infectionIL-1βInnate sensorsAdaptive immunityLike receptorsDetrimental pathologyI IFNAlveolar macrophagesHost responseImmune systemEfficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13910-13915. PMID: 23918369, PMCID: PMC3752242, DOI: 10.1073/pnas.1303275110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesFlow CytometryHistological TechniquesImmunity, InnateImmunohistochemistryInfluenza A virusMembrane GlycoproteinsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRespiratory Tract InfectionsSignal TransductionToll-Like Receptor 7Viral LoadVirus ReplicationConceptsToll-like receptor 7Innate immune responseRespiratory tractInfected wild-type miceHost innate immune responseAirways of miceViral target cellsWild-type miceAcid-inducible gene 1RIG-I pathwayPattern recognition receptorsHost innate defenseViral replication efficiencyInflammatory mediatorsBronchoalveolar lavageViral loadProinflammatory programProinflammatory responseReceptor 7IAV infectionInflammatory responseVirus infectionLow doseViral replicationVirus replication