2021
Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA
Ren X, Gelinas AD, Linehan M, Iwasaki A, Wang W, Janjic N, Pyle A. Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA. Journal Of Molecular Biology 2021, 433: 167227. PMID: 34487794, DOI: 10.1016/j.jmb.2021.167227.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, ViralAptamers, NucleotideBinding SitesCloning, MolecularCrystallography, X-RayDEAD Box Protein 58Escherichia coliGene ExpressionGenetic VectorsHumansImmunologic FactorsKineticsModels, MolecularMolecular MimicryMutationNucleic Acid ConformationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsReceptors, ImmunologicRecombinant ProteinsRNA, ViralSELEX Aptamer TechniqueConceptsHigh-resolution crystal structuresResolution crystal structureRIG-I receptorResult of mutationsSame amino acidsVertebrate organismsProtein receptorsInnate immune receptorsRNA virusesImmune receptorsAmino acidsTool compoundsViral ligandsViral RNAImportant receptorPathogenic moleculesGeneralizable strategyDNA aptamersMolecular mimicryCentral roleDisease statesReceptorsTerminusRNAOrganisms
2019
RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling. Cell Reports 2019, 29: 3807-3815.e3. PMID: 31851914, DOI: 10.1016/j.celrep.2019.11.052.Peer-Reviewed Original ResearchConceptsRNA moleculesRIG-I activationBase pair sequenceHost RNA moleculesViral RNA moleculesRIG-I recognitionMolecular basisRNA variantsRNA targetsPair sequenceHuman cellsBase pairsImmune receptorsMechanisms of evasionTerminal base pairsLigand affinityWhole animalInterferon responseDeadly pathogenRNA therapeuticsMarburg virusCellsOverhangMoleculesSignaling
2018
A minimal RNA ligand for potent RIG-I activation in living mice
Linehan MM, Dickey TH, Molinari ES, Fitzgerald ME, Potapova O, Iwasaki A, Pyle AM. A minimal RNA ligand for potent RIG-I activation in living mice. Science Advances 2018, 4: e1701854. PMID: 29492454, PMCID: PMC5821489, DOI: 10.1126/sciadv.1701854.Peer-Reviewed Original ResearchConceptsStem-loop RNAInterferon-stimulated genesImmune systemPotent synthetic activatorVertebrate immune systemType I interferonInnate immune systemRIG-I receptorRIG-I activationExpression networksRemodeling factorsPotent RIGRNA sequencingSpecific genesRNA ligandsI interferonAntiviral defenseInterferon responseRNA sensorsPolycytidylic acidSynthetic activatorsMiceInterferonGenesRNA
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingDEAD Box Protein 58FemaleHumansImmunity, InnateInterferonsMaleMonocytesReceptors, ImmunologicSignal TransductionConceptsType 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 cellsSensing Self and Foreign Circular RNAs by Intron Identity
Chen YG, Kim MV, Chen X, Batista PJ, Aoyama S, Wilusz JE, Iwasaki A, Chang HY. Sensing Self and Foreign Circular RNAs by Intron Identity. Molecular Cell 2017, 67: 228-238.e5. PMID: 28625551, PMCID: PMC5610545, DOI: 10.1016/j.molcel.2017.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceDEAD Box Protein 58Encephalitis Virus, Venezuelan EquineEncephalomyelitis, Venezuelan EquineHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmune ToleranceImmunity, InnateIntronsMiceNucleic Acid ConformationProtein BindingRAW 264.7 CellsReceptors, ImmunologicRNARNA Processing, Post-TranscriptionalRNA, CircularRNA, MessengerRNA-Binding ProteinsSpliceosomesTransfectionConceptsCircular RNAsInnate immunity genesMammalian transcriptionDiverse RNACytoplasmic fociHuman circRNAsMammalian cellsImmunity genesEndogenous splicingHuman intronsInnate immune sensingPrimary sequenceCircRNA sequenceRNA structureCircRNAsUnknown functionIntronsRNASensor RIGImmune sensingInnate immunitySelf-nonself discriminationPotent inductionSequenceBiogenesis
2012
A Virological View of Innate Immune Recognition
Iwasaki A. A Virological View of Innate Immune Recognition. Annual Review Of Microbiology 2012, 66: 177-196. PMID: 22994491, PMCID: PMC3549330, DOI: 10.1146/annurev-micro-092611-150203.Peer-Reviewed Original Research
2008
Innate sensors of influenza virus: clues to developing better intranasal vaccines
Ichinohe T, Iwasaki A, Hasegawa H. Innate sensors of influenza virus: clues to developing better intranasal vaccines. Expert Review Of Vaccines 2008, 7: 1435-1445. PMID: 18980544, PMCID: PMC2724183, DOI: 10.1586/14760584.7.9.1435.Peer-Reviewed Original ResearchConceptsInfluenza vaccineInnate sensorsVirus infectionImmune systemInfluenza virusIntranasal influenza vaccineVariant virus infectionNatural infectionEffective influenza vaccinesInfluenza virus infectionToll-like receptorsRetinoic acid-inducible geneNOD-like receptorsInnate immune systemPattern recognition receptorsAdaptive immune systemAcid-inducible geneParenteral immunizationIntranasal vaccineMucosal immunitySystemic immunityInactivated vaccinesRespiratory tractAdaptive immunityLike receptors
2004
Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
Sato A, Iwasaki A. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 16274-16279. PMID: 15534227, PMCID: PMC528964, DOI: 10.1073/pnas.0406268101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationCaspase 1Cell DifferentiationCell MovementDendritic CellsFemaleHerpesvirus 2, HumanImmunity, InnateInterleukin-12Membrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicReceptors, InterferonSignal TransductionStromal CellsTh1 CellsToll-Like ReceptorsConceptsToll-like receptorsT cell responsesPattern recognition receptorsViral infectionContribution of TLRsRecognition receptorsCell responsesEffector T cell responsesHerpes simplex virus type 2Simplex virus type 2Antiviral adaptive immunityDendritic cell compartmentEffector T cellsDendritic cell maturationMost viral infectionsVirus type 2Infected epithelial cellsMucosal infectionsT cellsAdaptive immunityAntiviral immunityInfectious agentsType 2Immune recognitionStromal cellsRecognition of single-stranded RNA viruses by Toll-like receptor 7
Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 5598-5603. PMID: 15034168, PMCID: PMC397437, DOI: 10.1073/pnas.0400937101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationBone Marrow CellsChick EmbryoChloroquineCytokinesDendritic CellsEndosomesInterferon-alphaMacrophagesMembrane GlycoproteinsMiceMice, KnockoutMyeloid Differentiation Factor 88OrthomyxoviridaePeritoneumReceptors, Cell SurfaceReceptors, ImmunologicRhabdoviridae InfectionsRNA, ViralSpleenToll-Like Receptor 7Vesicular stomatitis Indiana virusConceptsVesicular stomatitis virusRNA virusesHigh CpG contentGenomes of virusesToll-like receptorsStomatitis virusMammalian genomesGenomic nucleic acidsAdaptor protein MyD88Endocytic pathwayLigand recognitionCpG contentViral infectionTLR adaptor protein MyD88Innate immune responseToll-like receptor 7Molecular signaturesPlasmacytoid dendritic cellsInnate immune cellsProduction of cytokinesGenomeProtein MyD88Types of pathogensNucleic acidsVivo infection
2003
Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells. Journal Of Experimental Medicine 2003, 198: 513-520. PMID: 12900525, PMCID: PMC2194085, DOI: 10.1084/jem.20030162.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationBone Marrow CellsCpG IslandsDendritic CellsDNA-Binding ProteinsEndosomesFemaleHerpesvirus 2, HumanHumansInterferon-alphaMaleMiceMice, Inbred StrainsMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicSignal TransductionToll-Like Receptor 9ConceptsHerpes simplex virus 2Plasmacytoid dendritic cellsIFN-alpha secretionToll-like receptorsSimplex virus 2Dendritic cellsIFN-alphaI interferonToll-like receptor 9Virus 2Adaptor molecule MyD88Type I interferonHSV-2 DNADose-dependent mannerMouse bone marrowMolecule MyD88Receptor 9Knockout miceBone marrowTLR9Potent secretorsSecretionOligonucleotide treatmentVirus recognitionBafilomycin A1