2024
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virus
2023
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Proal A, VanElzakker M, Aleman S, Bach K, Boribong B, Buggert M, Cherry S, Chertow D, Davies H, Dupont C, Deeks S, Eimer W, Ely E, Fasano A, Freire M, Geng L, Griffin D, Henrich T, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter M, Peluso M, Pretorius E, Price D, Putrino D, Scheuermann R, Tan G, Tanzi R, VanBrocklin H, Yonker L, Wherry E. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology 2023, 24: 1616-1627. PMID: 37667052, DOI: 10.1038/s41590-023-01601-2.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsCOVID-19Disease ProgressionHumansPost-Acute COVID-19 SyndromeRNA, ViralSARS-CoV-2ConceptsSARS-CoV-2 reservoirPost-acute sequelaeImmune responseHost immune responseCoronavirus SARS-CoV-2COVID-19SARS-CoV-2Neuroimmune abnormalitiesAcute infectionLong COVIDClinical trialsViral RNAMillions of peopleSequelaeFurther studiesViral proteinsPathologyResearch prioritiesRNA/proteinBiological factorsPASCAntiviralsInfectionAbnormalitiesTrials
2022
Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration
Fiedler S, Devenish S, Morgunov A, Ilsley A, Ricci F, Emmenegger M, Kosmoliaptsis V, Theel E, Mills J, Sholukh A, Aguzzi A, Iwasaki A, Lynn A, Knowles T. Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration. Scientific Reports 2022, 12: 19791. PMID: 36396691, PMCID: PMC9672333, DOI: 10.1038/s41598-022-22214-z.Peer-Reviewed Original ResearchConceptsSerum antibody responseAntiviral activityHigh antiviral activityAntibody responseTherapeutic mAbsReduced antiviral activityVirus neutralization assaysSARS-CoV-2 virusSARS-CoV-2Convalescent individualsNeutralization assaysTherapeutic monoclonal antibodiesSame mAbMonoclonal antibodiesNew therapeuticsTherapeutic antibodiesMAbsAntibodiesRBDSotrovimabWild typeActivitySerumThe immunology and immunopathology of COVID-19
Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science 2022, 375: 1122-1127. PMID: 35271343, DOI: 10.1126/science.abm8108.Peer-Reviewed Original ResearchConceptsImmune responseAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionFatal COVID-19Coronavirus 2 infectionPost-acute sequelaeCOVID-19 pathophysiologyProlongation of symptomsLong COVID syndromeMajor unmet needCOVID-19SARS-CoV-2COVID syndromeDisease resolutionInflammatory processChronic illnessUnmet needDefinitive findingsImmunology researchCOVID-19 researchImmunopathologySequelaePathophysiologySyndrome
2021
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophagesIntranasal 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 protectionA stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacy
2020
Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19
Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19. The Journal Of Immunology 2020, 205: ji2000513. PMID: 32493814, PMCID: PMC7343621, DOI: 10.4049/jimmunol.2000513.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntiviral AgentsBetacoronavirusCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentHumansImmunity, InnateInflammasomesIntercellular Signaling Peptides and ProteinsMacrophages, AlveolarPandemicsPneumonia, ViralPyroptosisSARS-CoV-2Severe acute respiratory syndrome-related coronavirusSignal TransductionConceptsSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome-related coronavirus 2Coronavirus disease 2019 (COVID-19) patientsSevere coronavirus disease 2019Coronavirus 2 infectionAvailable pharmaceutical agentsCoronavirus disease 2019Innate immune pathwaysClinical outcomesCoronavirus 2Inflammatory responseCellular pyroptosisDisease 2019Downstream cytokinesInflammasome activationInflammasome pathwayTherapeutic targetImmune pathwaysPromising targetPharmaceutical agentsCOVID-19PyroptosisPatientsCytokinesInflammasomeType I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19
Park A, Iwasaki A. Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19. Cell Host & Microbe 2020, 27: 870-878. PMID: 32464097, PMCID: PMC7255347, DOI: 10.1016/j.chom.2020.05.008.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Role of interferonType ICoronavirus disease 2019COVID-19Innate antiviral responseOngoing global threatCoronavirus 2Pathogenic coronavirusesTreatment strategiesDisease 2019Protective effectHuman coronavirusesRecombinant interferonMERS-CoVSARS-CoVAntiviral responseInterferonAntiviral therapeuticsCombat COVID-19Interferon inductionGlobal pandemic
2013
Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts
Mattei LM, Cotmore SF, Tattersall P, Iwasaki A. Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts. Virology 2013, 442: 20-27. PMID: 23676303, PMCID: PMC3767977, DOI: 10.1016/j.virol.2013.03.020.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonIFN responseAntiviral immune mechanismsType I interferonInnate defense mechanismsMouse embryonic fibroblastsMVMp infectionViral controlImmune mechanismsInnate sensingAntiviral programViral replicationViral sensorsMurine parvovirusPoly (I:C) stimulationVirusEmbryonic fibroblastsType IMiceDefense mechanismsMinute virusMVMpPrimary mouse embryonic fibroblasts
2006
A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide
Shen H, Iwasaki A. A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide. Journal Of Clinical Investigation 2006, 116: 2237-2243. PMID: 16878177, PMCID: PMC1518794, DOI: 10.1172/jci28681.Peer-Reviewed Original ResearchConceptsCpG ODNPlasmacytoid DCsHerpes simplex virus type 2Simplex virus type 2Lethal vaginal challengeVaginal stromal cellsPlasmacytoid dendritic cellsGenital herpes infectionIFN-alphabeta receptorAssociated inflammatory responseVirus type 2Vaginal challengeDendritic cellsHerpes infectionTLR agonistsMicrobicide efficacyTopical microbicidesVaginal microbicidesInflammatory responseI IFNAntiviral protectionType 2Antiviral genesStromal compartmentVaginal application