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 I
2016
Two 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
2014
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux A, Jackson R, Harman CC, Li T, West AP, de Zoete MR, Wu Y, Yordy B, Lakhani SA, Kuan CY, Taniguchi T, Shadel GS, Chen ZJ, Iwasaki A, Flavell RA. Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA. Cell 2014, 159: 1563-1577. PMID: 25525875, PMCID: PMC4272443, DOI: 10.1016/j.cell.2014.11.037.Peer-Reviewed Original ResearchConceptsMitochondrial outer membrane permeabilizationCell deathOuter membrane permeabilizationType I interferonDNA-dependent activationCaspase-dependent mannerI interferonCGAS/STING pathwayMitochondrial DNAApoptotic caspasesMembrane permeabilizationActive caspasesProapoptotic caspasesMitochondriaCaspasesSTING pathwayIFN responseAntiviral immunityCentral roleDual controlPathwayProinflammatory typeInductionCellsActivationEpigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth
Ding S, Khoury-Hanold W, Iwasaki A, Robek MD. Epigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth. PLOS Biology 2014, 12: e1001758. PMID: 24409098, PMCID: PMC3883642, DOI: 10.1371/journal.pbio.1001758.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCpG IslandsCricetinaeCytomegalovirusDNA MethylationEpigenesis, GeneticHepatocytesHerpesvirus 1, HumanHistone Deacetylase InhibitorsHistone DeacetylasesHost-Pathogen InteractionsHumansInterferon-gammaMiceNIH 3T3 CellsOrgan SpecificityPromoter Regions, GeneticReceptors, CytokineReceptors, InterferonRNA, Small InterferingSignal TransductionVesiculovirusConceptsHDAC inhibitorsPro-apoptotic activityRepression machineryExpression programsTranscriptional silencingEpigenetic reprogrammingEpigenetic rewiringUbiquitous expressionMolecular mechanismsCell typesSpecific mannerSuppress tumor growthReceptor subunitsPotential antitumor strategyNonresponsive cellsIFN responseAntiviral immunityViral pathogensExpressionReceptor expressionType III interferonsAntitumor strategyΒ receptorTumor growthEpithelial origin