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 macrophagesHigh-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
Haynes WA, Kamath K, Bozekowski J, Baum-Jones E, Campbell M, Casanovas-Massana A, Daugherty PS, Dela Cruz CS, Dhal A, Farhadian SF, Fitzgibbons L, Fournier J, Jhatro M, Jordan G, Klein J, Lucas C, Kessler D, Luchsinger LL, Martinez B, Catherine Muenker M, Pischel L, Reifert J, Sawyer JR, Waitz R, Wunder EA, Zhang M, Iwasaki A, Ko A, Shon J. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Communications Biology 2021, 4: 1317. PMID: 34811480, PMCID: PMC8608966, DOI: 10.1038/s42003-021-02835-2.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 antibodiesRespiratory syndrome coronavirus 2SARS-CoV-2 epitopesSyndrome coronavirus 2SARS-CoV-2 strainsHigh-resolution epitope mappingCOVID-19SARS-CoV-2SARS-CoV-2 mutantsCoronavirus 2Antibody responseEffective vaccineImmune responseNeutralization activitySevere diseaseLarge cohortEpitope regionsAntibody epitopesEpitope mappingRelated coronavirusesTherapyVaccineViral proteomeA 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 efficacySex differences in immune responses
Takahashi T, Iwasaki A. Sex differences in immune responses. Science 2021, 371: 347-348. PMID: 33479140, DOI: 10.1126/science.abe7199.Peer-Reviewed Original ResearchConceptsImmune responseCOVID-19Sex differencesSevere COVID-19Risk of deathHigher mortality riskCOVID-19 mortalityPossible biological mechanismsCOVID-19 incidenceMale sexRisk factorsSevere diseaseHigh riskMortality riskMale sex biasOld maleSex-disaggregated dataBehavioral factorsBiological sex differencesDeathVulnerable groupsRiskBiological mechanismsMalesSex
2019
Low 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 virus
2018
Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development
Yockey LJ, Iwasaki A. Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development. Immunity 2018, 49: 397-412. PMID: 30231982, PMCID: PMC6152841, DOI: 10.1016/j.immuni.2018.07.017.Peer-Reviewed Original ResearchConceptsFetal developmentHealthy pregnancyImmune responseFetal immune responseRole of interferonPregnancy complicationsProinflammatory cytokinesSuccessful pregnancyCertain infectionsPregnant mothersImmune cellsInflammatory conditionsSevere diseasePregnancyFetal diseaseImmune systemCytokinesCongenital disorderPossible targetsInterferonFetusesInfectionDiseaseMothersComplications
2010
Antiviral immune responses in the genital tract: clues for vaccines
Iwasaki A. Antiviral immune responses in the genital tract: clues for vaccines. Nature Reviews Immunology 2010, 10: 699-711. PMID: 20829886, PMCID: PMC3678359, DOI: 10.1038/nri2836.Peer-Reviewed Original ResearchConceptsGenital mucosaT cellsGenital tractHerpes simplex virus type 2Simplex virus type 2Innate immune cellsT cell populationsAntiviral immune responseFemale genital tractPattern recognition receptorsVirus type 2Immune correlatesMemory CD4Memory CD8Viral clearanceHuman papillomavirusImmune cellsMemory lymphocytesSuccessful vaccineHIV-1Immune responseSevere diseaseVaginal epitheliumAdaptive immunityTarget cell type