2022
Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion
Vora SM, Fontana P, Mao T, Leger V, Zhang Y, Fu TM, Lieberman J, Gehrke L, Shi M, Wang L, Iwasaki A, Wu H. Targeting stem-loop 1 of the SARS-CoV-2 5′ UTR to suppress viral translation and Nsp1 evasion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2117198119. PMID: 35149555, PMCID: PMC8892331, DOI: 10.1073/pnas.2117198119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 nonstructural protein 1Host protein synthesisSARS-CoV-2 5Nonstructural protein 1Viral translationNucleic acid antisenseAntiviral immunityProtein synthesisTherapeutic targetTransgenic miceViral protein synthesisViral replicationDrug resistanceHuman ACE2Infected cellsProtein 1COVID-19Virulence mechanismsNanomolar concentrationsHost translationPathogenic virusesEntry channelSuppressionTranslational suppression
2021
Prevention of host-to-host transmission by SARS-CoV-2 vaccines
Mostaghimi D, Valdez CN, Larson HT, Kalinich CC, Iwasaki A. Prevention of host-to-host transmission by SARS-CoV-2 vaccines. The Lancet Infectious Diseases 2021, 22: e52-e58. PMID: 34534512, PMCID: PMC8439617, DOI: 10.1016/s1473-3099(21)00472-2.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 vaccinesSymptomatic COVID-19Population-level dataVaccine's abilityIntramuscular vaccineImmunological mechanismsVaccine strategiesVaccine capacityPrimary infectionNatural courseClinical trialsObservational studyRespiratory epitheliumReal-world settingViral titresViral replicationVaccineVaccine distributionInfectionCOVID-19Host transmissionTrialsPopulation-level effectsMucosaSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
2018
An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication
Orzalli MH, Smith A, Jurado KA, Iwasaki A, Garlick JA, Kagan JC. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Molecular Cell 2018, 71: 825-840.e6. PMID: 30100266, PMCID: PMC6411291, DOI: 10.1016/j.molcel.2018.07.009.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsIL-1Host-derived damage-associated molecular patternsViral replicationVirus replicationInfected cellsInterleukin-1 family cytokinesIL-1 Signaling PathwayInflammatory gene expressionIL-1 actsHuman skin explantsProtective immunityIL-1αBarrier defenseInflammatory signalsViral infectionFamily cytokinesSkin explantsGene expressionMolecular patternsSkin fibroblastsSignaling pathwaysAntiviral systemBarrier epitheliaCell types
2017
IRE1α promotes viral infection by conferring resistance to apoptosis
Fink SL, Jayewickreme TR, Molony RD, Iwawaki T, Landis CS, Lindenbach BD, Iwasaki A. IRE1α promotes viral infection by conferring resistance to apoptosis. Science Signaling 2017, 10 PMID: 28588082, PMCID: PMC5535312, DOI: 10.1126/scisignal.aai7814.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCase-Control StudiesCells, CulturedEndoribonucleasesFemaleHepacivirusHepatitis CHerpes SimplexHumansLiverMaleMiceMice, KnockoutMicroRNAsProtein Serine-Threonine KinasesSimplexvirusVesicular StomatitisVesicular stomatitis Indiana virusViral Nonstructural ProteinsVirus ReplicationX-Box Binding Protein 1ConceptsX-box binding protein 1Type I IFN responseI IFN responseUnfolded protein responseViral-induced apoptosisActivation of IRE1αLiver biopsyAntiviral therapyHealthy controlsAntiviral resistanceViral infectionBinding protein 1Antiapoptotic Bcl-2 familyIFN responseViral replicationDeficient cellsProtein 1Apoptosis resistancePossible targetsProsurvival roleEnzyme 1αApoptosisInfectionIntrinsic pathwayType ITAM 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
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 consequencesTwo interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature
Foxman EF, Storer JA, Vanaja K, Levchenko A, Iwasaki A. Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8496-8501. PMID: 27402752, PMCID: PMC4968739, DOI: 10.1073/pnas.1601942113.Peer-Reviewed Original ResearchConceptsIFN-independent mechanismsEpithelial cellsHost defense strategiesHost cell deathIFN inductionHuman bronchial epithelial cellsReduced virus productionCommon cold virusInfected epithelial cellsB-cell lymphoma 2 (Bcl-2) overexpressionBronchial epithelial cellsDiverse stimuliViral replicationAntiviral pathwaysCell deathH1-HeLa cellsTemperature-dependent replicationCell typesSingle replication cycleTemperature-dependent growthReplication cycleWarmer temperaturesCool temperaturesDefense strategiesType 1 IFN response
2015
Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells
Foxman EF, Storer JA, Fitzgerald ME, Wasik BR, Hou L, Zhao H, Turner PE, Pyle AM, Iwasaki A. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 827-832. PMID: 25561542, PMCID: PMC4311828, DOI: 10.1073/pnas.1411030112.Peer-Reviewed Original ResearchConceptsAirway cellsCommon cold virusViral replicationIFN inductionRecombinant type I IFNMouse airway epithelial cellsCold virusAirway epithelial cellsInduction of ISGsType I IFNPrimary airway cellsCore body temperatureType IAntiviral defense responseLike receptorsI IFNNasal cavityMAVS proteinHuman rhinovirusSustained increaseInnate defensePoly IGenetic deficiencyRobust inductionRhinovirus
2013
Efficient 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 replicationParvovirus 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
2012
A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus
Yordy B, Iijima N, Huttner A, Leib D, Iwasaki A. A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus. Cell Host & Microbe 2012, 12: 334-345. PMID: 22980330, PMCID: PMC3454454, DOI: 10.1016/j.chom.2012.07.013.Peer-Reviewed Original ResearchConceptsI interferonHSV-1 replicationDorsal root ganglionic neuronsType I IFN treatmentHerpes simplex type 1I IFN treatmentI IFNsHSV-1 infectionHerpes simplex virusNeuron-specific rolesSimplex type 1Type I interferonMucosal epithelial cellsDRG neuronsGanglionic neuronsNeurotropic virusesIFN treatmentSimplex virusViral infectionAntiviral pathwaysViral replicationType 1Antiviral strategiesLittle type INeurons
2011
Mitoxosome: a mitochondrial platform for cross‐talk between cellular stress and antiviral signaling
Tal MC, Iwasaki A. Mitoxosome: a mitochondrial platform for cross‐talk between cellular stress and antiviral signaling. Immunological Reviews 2011, 243: 215-234. PMID: 21884179, PMCID: PMC3170140, DOI: 10.1111/j.1600-065x.2011.01038.x.Peer-Reviewed Original ResearchConceptsCellular stressMitochondrial functionCell biologic analysesViral recognitionInnate immune signalingDynamic relocalizationAntiviral signalingImmune signalingMitochondriaAntiviral responseMultiple pathwaysAntiviral immunityCurrent understandingRecent findingsSignalingViral replicationInnate responseIntegrated viewBiologic analysisRecent studiesSignalosomeRelocalizationKey componentStressIntegral platform
2008
Autophagy and antiviral immunity
Lee HK, Iwasaki A. Autophagy and antiviral immunity. Current Opinion In Immunology 2008, 20: 23-29. PMID: 18262399, PMCID: PMC2271118, DOI: 10.1016/j.coi.2008.01.001.Peer-Reviewed Original ResearchConceptsViral infectionViral replicationAdaptive antiviral immune responsesEndogenous viral antigensCD4 T cellsMHC class II loading compartmentsAntiviral immune responseCritical effector mechanismAdaptive immune systemViral antigensEffector mechanismsT cellsImmune responseAntiviral immunityImmune systemLoading compartmentCertain virusesInfectionAutophagyRecent studiesCellsAntigenImmunityCellular homeostasis
2007
Role of Autophagy in Innate Viral Recognition
Iwasaki A. Role of Autophagy in Innate Viral Recognition. Autophagy 2007, 3: 354-356. PMID: 17404496, DOI: 10.4161/auto.4114.Peer-Reviewed Original ResearchConceptsPlasmacytoid dendritic cellsToll-like receptorsI interferonViral recognitionLive viral infectionType I interferonRole of autophagyPDC responsesDendritic cellsViral infectionViral replicationTLR7Pathogen signaturesVirusSuch virusesVirus detectionAutophagyRNA virusesRecent studiesInterferonInfectionSsRNA virusesSecretionReceptorsAutophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells. Science 2007, 315: 1398-1401. PMID: 17272685, DOI: 10.1126/science.1136880.Peer-Reviewed Original ResearchConceptsPlasmacytoid dendritic cellsToll-like receptorsDendritic cellsInterferon-alpha secretionLive viral infectionPDC responsesViral infectionViral recognitionViral replicationPathogen signaturesTLR7VirusSuch virusesVirus detectionProcess of autophagyAutophagyRNA virusesCellsInfectionPresent evidenceSecretionReceptors
2006
Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ
Lund JM, Linehan MM, Iijima N, Iwasaki A. Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ. The Journal Of Immunology 2006, 177: 7510-7514. PMID: 17114418, DOI: 10.4049/jimmunol.177.11.7510.Peer-Reviewed Original ResearchConceptsMucosal viral infectionsPlasmacytoid dendritic cellsPlasmacytoid DCsDendritic cellsViral infectionGenital HSV-2 infectionHSV-2 infectionLocal viral replicationAntiviral effector cellsInnate immune protectionTLR9-dependent mannerType I IFNsType I IFNPeripheral mucosaPowerful APCsTh1 immunityEffector cellsImmune protectionNaive lymphocytesAdaptive immunityI IFNsI IFNVaginal mucosaViral replicationInnate defense