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
2019
Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice
Treger RS, Tokuyama M, Dong H, Salas-Briceno K, Ross SR, Kong Y, Iwasaki A. Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00728-19. PMID: 31341050, PMCID: PMC6798113, DOI: 10.1128/jvi.00728-19.Peer-Reviewed Original ResearchConceptsToll-like receptor 7Infectious endogenous retrovirusHuman APOBEC3GAPOBEC3GHA3GEndogenous retrovirusesAntiviral restriction factorsReceptor 7Human endogenous retrovirusesTransgenic miceERV RNAsERV reactivationMiceAPOBEC3 proteinsCell-intrinsic defenseHost mechanismsPrevents emergenceRestriction factorsPermissive cellsDeleterious consequencesSubsequent disruptionRetrovirusesEctopic expressionHumansExpression
2017
Sensing 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
2015
Tissue instruction for migration and retention of TRM cells
Iijima N, Iwasaki A. Tissue instruction for migration and retention of TRM cells. Trends In Immunology 2015, 36: 556-564. PMID: 26282885, PMCID: PMC4567393, DOI: 10.1016/j.it.2015.07.002.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsMemory lymphocyte clustersTRM cellsT cellsCD4 tissue-resident memory T cellsRobust local immune responseCD8 TRM cellsEffector T cellsLocal immune responseMemory T cellsNon-lymphoid tissuesLymphocyte clustersImmune responseInfectious agentsIncoming pathogensCell homingRecent findingsCellsInfectionFindingsCervicovaginal Microbiota: Simple Is Better
Gopinath S, Iwasaki A. Cervicovaginal Microbiota: Simple Is Better. Immunity 2015, 42: 790-791. PMID: 25992855, DOI: 10.1016/j.immuni.2015.05.006.Peer-Reviewed Original Research
2014
Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function
Guo YE, Riley KJ, Iwasaki A, Steitz JA. Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function. Molecular Cell 2014, 54: 67-79. PMID: 24725595, PMCID: PMC4039351, DOI: 10.1016/j.molcel.2014.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteBase SequenceCallithrixEnzyme ActivationGene Expression RegulationGPI-Linked ProteinsGRB2 Adaptor ProteinHEK293 CellsHerpesvirus 2, SaimiriineHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansImmunoprecipitationInterferon-gammaJurkat CellsLectins, C-TypeLymphocyte ActivationMicroRNAsMitogen-Activated Protein KinasesMolecular Sequence DataReceptors, Antigen, T-CellRNA StabilityRNA, UntranslatedRNA, ViralSemaphorinsSequence Analysis, RNASignal TransductionTime FactorsT-LymphocytesTransfectionConceptsMitogen-activated protein kinaseMiR-27Protein coding genesHerpesvirus saimiriHigh-throughput sequencingTCR-induced activationCell functionHSUR 1Γ-herpesvirusesNoncoding RNAsProtein kinaseEctopic expressionOncogenic γ-herpesvirusesTarget genesInduction of CD69MicroRNA-27Key modulatorRNACommon targetAlHV-1GenesCell receptorDiverse strategiesHost T-cell functionCellsEpigenetic 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
2013
ELF4 is critical for induction of type I interferon and the host antiviral response
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology 2013, 14: 1237-1246. PMID: 24185615, PMCID: PMC3939855, DOI: 10.1038/ni.2756.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDNA-Binding ProteinsHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmunoblottingInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSurvival AnalysisTranscription FactorsTranscriptional ActivationWest Nile FeverWest Nile virus
2012
Autophagy and selective deployment of Atg proteins in antiviral defense
Yordy B, Tal MC, Hayashi K, Arojo O, Iwasaki A. Autophagy and selective deployment of Atg proteins in antiviral defense. International Immunology 2012, 25: 1-10. PMID: 23042773, PMCID: PMC3534236, DOI: 10.1093/intimm/dxs101.Peer-Reviewed Original ResearchConceptsAutophagy machineryAtg proteinsAntiviral defenseViral pathogen-associated molecular patternsPathogen-associated molecular patternsEukaryotic cellsCellular homeostasisCanonical autophagyViral replication sitesMajor histocompatibility complex presentationIntracellular transportAntiviral proteinCytosolic componentsRegulatory functionsEndolysosomal compartmentsReplication sitesAutophagyMachineryMolecular patternsDiverse repertoireIntracellular materialProteinToll-like receptorsViral antigen processingSelective targetingInnate Immune Recognition of HIV-1
Iwasaki A. Innate Immune Recognition of HIV-1. Immunity 2012, 37: 389-398. PMID: 22999945, PMCID: PMC3578946, DOI: 10.1016/j.immuni.2012.08.011.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesDendritic CellsHIV InfectionsHIV-1Host-Pathogen InteractionsHumansImmunity, InnateModels, ImmunologicalToll-Like ReceptorsPhagosome as the Organelle Linking Innate and Adaptive Immunity
Kagan JC, Iwasaki A. Phagosome as the Organelle Linking Innate and Adaptive Immunity. Traffic 2012, 13: 1053-1061. PMID: 22577865, PMCID: PMC3658133, DOI: 10.1111/j.1600-0854.2012.01377.x.Peer-Reviewed Original ResearchConceptsProcess of phagocytosisPhagosome traffickingAdaptive immunityAntimicrobial defense mechanismsDefinable unitSubcellular levelT cell-mediated immunityAdaptive immune systemDefense mechanismsToll-like receptorsPhagosomesPhagocytosisImmune systemImmunityMicrobesTraffickingAutophagyPathwayReceptorsInnate
2011
Genome–virome interactions: examining the role of common viral infections in complex disease
Foxman EF, Iwasaki A. Genome–virome interactions: examining the role of common viral infections in complex disease. Nature Reviews Microbiology 2011, 9: 254-264. PMID: 21407242, PMCID: PMC3678363, DOI: 10.1038/nrmicro2541.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHuman genetic variationLarge regulatory networkHost-virus interactionsCrohn's diseaseRegulatory networksHost genesGenetic variationModel hostGenomic technologiesAutophagy pathwayAntiviral defenseViral infectionAdditional host factorsEnvironmental conditionsComplex diseasesCommon viral infectionsCases of asthmaSubsequent disease developmentGenesHostHost factorsDisease developmentParticular virusMicrobiota regulates immune defense against respiratory tract influenza A virus infection
Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 5354-5359. PMID: 21402903, PMCID: PMC3069176, DOI: 10.1073/pnas.1019378108.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionVirus infectionDendritic cellsImmune responseCommensal bacteriaRespiratory influenza virus infectionToll-like receptor ligandsVirus-specific CD4CD8 T cellsT cell primingCommensal microbiota compositionProductive immune responseExpression of mRNADistal injectionLymph nodesImmune impairmentIntact microbiotaIL-1βAntibody responseImmune homeostasisRespiratory mucosaAntibiotic treatmentT cellsInflammasome activationCommensal microbiota
2007
Toll-like receptors regulation of viral infection and disease
Thompson JM, Iwasaki A. Toll-like receptors regulation of viral infection and disease. Advanced Drug Delivery Reviews 2007, 60: 786-794. PMID: 18280610, PMCID: PMC2410298, DOI: 10.1016/j.addr.2007.11.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHost-Pathogen InteractionsHumansReceptors, VirusToll-Like ReceptorsVirus DiseasesVirusesConceptsToll-like receptorsVirus infectionRole of TLRsProtective anti-viral immunityToll-like receptor regulationAdaptive immune responsesAnti-viral immunityMammalian Toll-like receptorsVirus-induced diseaseViral nucleic acidsStudies of miceTLR activationInteraction of virusImmune responseViral infectionTLR systemTLR proteinsReceptor regulationInfectionDiseaseOutcomesCritical roleMiceImmunityReceptors