2019
Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat
Taura M, Song E, Ho YC, Iwasaki A. Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 2282-2289. PMID: 30670656, PMCID: PMC6369738, DOI: 10.1073/pnas.1819386116.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCell LineCytidine DeaminaseEpigenesis, GeneticGene Expression Regulation, ViralGene SilencingHIV InfectionsHIV Long Terminal RepeatHIV-1HumansNF-kappa BProtein BindingProtein Interaction Domains and MotifsProteinsSequence DeletionSp1 Transcription FactorVirus ActivationVirus LatencyConceptsHIV-1 latencyHIV-1 reactivationCD4 T cellsT cellsHuman primary CD4 T cellsInfected CD4 T cellsHIV-1-infected cellsPrimary CD4 T cellsLong terminal repeat regionHIV-1Therapeutic strategiesLower reactivationProviral DNALatency maintenanceTarget cellsLatency stateCell linesLong terminal repeatTerminal repeat regionMolecular mechanismsReactivationCellsKnockdownA3AUnexpected role
2018
ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses
Tokuyama M, Kong Y, Song E, Jayewickreme T, Kang I, Iwasaki A. ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 12565-12572. PMID: 30455304, PMCID: PMC6294949, DOI: 10.1073/pnas.1814589115.Peer-Reviewed Original ResearchConceptsEndogenous retrovirusesGenome-wide identificationProtein-coding sequencesLocus-specific expressionWide transcriptionHuman genomeHuman endogenous retrovirusesERV lociExpression patternsRetroviral elementsPrimary cellsPeripheral blood mononuclear cellsRange of diseasesBreast cancer tissue samplesHuman healthSystemic lupus erythematosusBlood mononuclear cellsCancer tissue samplesDisease-associated antigensCell linesRNALack of toolsWeb toolLupus erythematosusPerforin expressionRegional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Mihaylova VT, Kong Y, Fedorova O, Sharma L, Dela Cruz CS, Pyle AM, Iwasaki A, Foxman EF. Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. Cell Reports 2018, 24: 3000-3007.e3. PMID: 30208323, PMCID: PMC6190718, DOI: 10.1016/j.celrep.2018.08.033.Peer-Reviewed Original ResearchConceptsRIG-I stimulationAntiviral responseRhinovirus infectionBronchial airway epithelial cellsAcute respiratory infectionsEpithelial cellsRobust antiviral responseAirway epithelial cellsPrimary human nasalAirway damageRespiratory infectionsAirway microenvironmentAsthma attacksNasal mucosaLeading causeNrf2 knockdownNasal cellsNrf2 activationHuman nasalEpithelial defenseHost defenseBronchial cellsInfectionOxidative stressRhinovirusAn 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 typesKDM5 histone demethylases repress immune response via suppression of STING
Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, Shadel GS, Yan Q. KDM5 histone demethylases repress immune response via suppression of STING. PLOS Biology 2018, 16: e2006134. PMID: 30080846, PMCID: PMC6095604, DOI: 10.1371/journal.pbio.2006134.Peer-Reviewed Original ResearchConceptsImmune responseSTING expressionCyclic GMP-AMP synthase stimulatorSuppression of STINGCancer cellsCancer immunotherapy agentsHuman papilloma virusAdaptive immune responsesMultiple clinical trialsExpression of STINGBreast cancer cellsInnate immune defenseRobust interferon responseMultiple cancer typesIntratumoral CD8Immunotherapy agentsAnticancer immunotherapyPatient survivalNeck cancerPapilloma virusClinical trialsT cellsSTING agonistsKDM5 histonePositive head
2017
The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry
Lipovsky A, Erden A, Kanaya E, Zhang W, Crite M, Bradfield C, MacMicking J, DiMaio D, Schoggins JW, Iwasaki A. The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry. Journal Of General Virology 2017, 98: 2821-2836. PMID: 29058661, PMCID: PMC5845663, DOI: 10.1099/jgv.0.000954.Peer-Reviewed Original ResearchConceptsHuman papillomavirusEntry of HPVVirus entryImportant infectious causeL1 major capsid proteinHPV typesTrans-Golgi networkInfectious causesProphylactic vaccinesHPV16 infectionL2 minor capsid proteinHPV entryDeadly cancerHPV16 entryBasal levelsInfectionVirus uptakeRetrograde transportHuman keratinocytesCapsid proteinHPV16PapillomavirusVirus uncoatingNon-enveloped virusesVirus
2015
Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity
Hayashi K, Sasai M, Iwasaki A. Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity. International Immunology 2015, 27: 435-445. PMID: 25925170, PMCID: PMC4560039, DOI: 10.1093/intimm/dxv021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell MembraneDendritic CellsDNA-Binding ProteinsEndosomesInterferon Type ILysosome-Associated Membrane GlycoproteinsMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesProtein TransportSignal TransductionToll-Like Receptor 7Toll-Like Receptor 9Transcription FactorsVesicle-Associated Membrane Protein 3ConceptsDifferent dendritic cell subsetsIFN inductionDendritic cell subsetsInduction of cytokinesType I IFN inductionType I IFNType I interferonI IFN inductionViral nucleic acidsAnti-viral programsTLR9 traffickingCell subsetsTLR9 signalsI IFNI interferonInhibitor treatmentDistinct subcellular membranesRAW264.7 cellsType I interferon (IFN) genesTLR9Distinct endosomal compartmentsInterferon genesTLR traffickingConfocal microscopyInductionMitochondrial DNA stress primes the antiviral innate immune response
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520: 553-557. PMID: 25642965, PMCID: PMC4409480, DOI: 10.1038/nature14156.Peer-Reviewed Original Research
2014
Application of the Proximity-Dependent Assay and Fluorescence Imaging Approaches to Study Viral Entry Pathways
Lipovsky A, Zhang W, Iwasaki A, DiMaio D. Application of the Proximity-Dependent Assay and Fluorescence Imaging Approaches to Study Viral Entry Pathways. Methods In Molecular Biology 2014, 1270: 437-451. PMID: 25702134, DOI: 10.1007/978-1-4939-2309-0_30.Peer-Reviewed Original ResearchConceptsGenome-wide RNA interference screenEnriched gene categoriesConfirmation of phenotypesGenome-wide lossRNA interference screenVirus entryFunction genetic screenRNA interference studiesFluorescence imaging approachesProximity ligation assayGenetic screenGene categoriesInterference screenMembrane compartmentsIndividual genesBiochemical approachesCellular compartmentsMolecular intricaciesMicroscopy-based methodBioinformatics analysisProtein locationRNA interferenceCellular organellesViral entry pathwayCellular factors
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
2006
Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells
Sato A, Linehan MM, Iwasaki A. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 17343-17348. PMID: 17085599, PMCID: PMC1859932, DOI: 10.1073/pnas.0605102103.Peer-Reviewed Original ResearchConceptsToll-like receptorsHerpes simplex virusMultiple Toll-like receptorsDendritic cellsSimplex virusBone marrow-derived dendritic cellsMarrow-derived dendritic cellsMultiple pathogen-associated molecular patternsPrimary clinical isolatesIL-12 secretionConventional dendritic cellsSame dendritic cellInnate immune systemPathogen-associated molecular patternsViral infection resultsProinflammatory cytokinesSurface TLR2IL-6Infection resultsTLR2TLR9Viral recognitionImmune systemClinical isolatesAdditional agonists