2023
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Proal A, VanElzakker M, Aleman S, Bach K, Boribong B, Buggert M, Cherry S, Chertow D, Davies H, Dupont C, Deeks S, Eimer W, Ely E, Fasano A, Freire M, Geng L, Griffin D, Henrich T, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter M, Peluso M, Pretorius E, Price D, Putrino D, Scheuermann R, Tan G, Tanzi R, VanBrocklin H, Yonker L, Wherry E. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nature Immunology 2023, 24: 1616-1627. PMID: 37667052, DOI: 10.1038/s41590-023-01601-2.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsCOVID-19Disease ProgressionHumansPost-Acute COVID-19 SyndromeRNA, ViralSARS-CoV-2ConceptsSARS-CoV-2 reservoirPost-acute sequelaeImmune responseHost immune responseCoronavirus SARS-CoV-2COVID-19SARS-CoV-2Neuroimmune abnormalitiesAcute infectionLong COVIDClinical trialsViral RNAMillions of peopleSequelaeFurther studiesViral proteinsPathologyResearch prioritiesRNA/proteinBiological factorsPASCAntiviralsInfectionAbnormalitiesTrials
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 statesReceptorsTerminusRNAOrganismsStability of SARS-CoV-2 RNA in Nonsupplemented Saliva - Volume 27, Number 4—April 2021 - Emerging Infectious Diseases journal - CDC
Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC, Harden CA, Vogels CBF, Casanovas-Massana A, Moore AJ, Muenker MC, Nakahata M, Tokuyama M, Nelson A, Fournier J, Bermejo S, Campbell M, Datta R, Dela Cruz CS, Farhadian SF, Ko AI, Iwasaki A, Grubaugh ND, Wilen CB, Wyllie AL, . Stability of SARS-CoV-2 RNA in Nonsupplemented Saliva - Volume 27, Number 4—April 2021 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2021, 27: 1146-1150. PMID: 33754989, PMCID: PMC8007305, DOI: 10.3201/eid2704.204199.Peer-Reviewed Original Research
2020
Detection of SARS-CoV-2 RNA by multiplex RT-qPCR
Kudo E, Israelow B, Vogels CBF, Lu P, Wyllie AL, Tokuyama M, Venkataraman A, Brackney DE, Ott IM, Petrone ME, Earnest R, Lapidus S, Muenker MC, Moore AJ, Casanovas-Massana A, Team Y, Omer SB, Dela Cruz CS, Farhadian SF, Ko AI, Grubaugh ND, Iwasaki A. Detection of SARS-CoV-2 RNA by multiplex RT-qPCR. PLOS Biology 2020, 18: e3000867. PMID: 33027248, PMCID: PMC7571696, DOI: 10.1371/journal.pbio.3000867.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusCase-Control StudiesClinical Laboratory TechniquesCoronavirus InfectionsCOVID-19COVID-19 TestingDNA PrimersHEK293 CellsHumansLimit of DetectionMultiplex Polymerase Chain ReactionNasopharynxPandemicsPneumonia, ViralReagent Kits, DiagnosticReverse Transcriptase Polymerase Chain ReactionRNA, ViralSARS-CoV-2United StatesConceptsSARS-CoV-2 RNAMultiplex RT-qPCRRT-qPCRSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingSARS-CoV-2Quantitative reverse transcription PCRCycle threshold valuesReverse transcription-PCRRT-qPCR assaysDisease controlMultiplex RT-qPCR assayTranscription-PCRAssaysSingle assayLow copy numberSex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesSARS-CoV-2 infection of the placenta
Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels C, Casanovas-Massana A, Vijayakumar P, Geng B, Odio CD, Fournier J, Brito AF, Fauver JR, Liu F, Alpert T, Tal R, Szigeti-Buck K, Perincheri S, Larsen C, Gariepy AM, Aguilar G, Fardelmann KL, Harigopal M, Taylor HS, Pettker CM, Wyllie AL, Dela Cruz CS, Ring AM, Grubaugh ND, Ko AI, Horvath TL, Iwasaki A, Reddy UM, Lipkind HS. SARS-CoV-2 infection of the placenta. Journal Of Clinical Investigation 2020, 130: 4947-4953. PMID: 32573498, PMCID: PMC7456249, DOI: 10.1172/jci139569.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAbortion, TherapeuticAbruptio PlacentaeAdultBetacoronavirusCoronavirus InfectionsCOVID-19FemaleHumansMicroscopy, Electron, TransmissionPandemicsPhylogenyPlacentaPneumonia, ViralPre-EclampsiaPregnancyPregnancy Complications, InfectiousPregnancy Trimester, SecondRNA, ViralSARS-CoV-2Viral LoadConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 invasionMaternal antibody responseSymptomatic COVID-19Second trimester pregnancySyndrome coronavirus 2Coronavirus disease 2019Materno-fetal interfaceDense macrophage infiltratesPlacental abruptionSevere preeclampsiaMacrophage infiltratesSevere morbidityTrimester pregnancyPregnant womenCoronavirus 2Antibody responseBackgroundThe effectsDisease 2019Histological examinationImmunohistochemical assaysPlacentaAnalytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets
Vogels CBF, Brito AF, Wyllie AL, Fauver JR, Ott IM, Kalinich CC, Petrone ME, Casanovas-Massana A, Catherine Muenker M, Moore AJ, Klein J, Lu P, Lu-Culligan A, Jiang X, Kim DJ, Kudo E, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Tokuyama M, Venkataraman A, Weizman OE, Wong P, Yang Y, Cheemarla NR, White EB, Lapidus S, Earnest R, Geng B, Vijayakumar P, Odio C, Fournier J, Bermejo S, Farhadian S, Dela Cruz CS, Iwasaki A, Ko AI, Landry ML, Foxman EF, Grubaugh ND. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5: 1299-1305. PMID: 32651556, PMCID: PMC9241364, DOI: 10.1038/s41564-020-0761-6.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 RTSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral RNA copiesPublic health laboratoriesPublic health interventionsReverse transcription-PCR assaySARS-CoV-2 diagnostic testingDiagnostic assaysTranscription-PCR assaySARS-CoV-2 evolutionQuantitative reverse transcription-PCR assaysRapid diagnostic assaysHealth laboratoriesHealth interventionsDiagnostic testingRNA copiesPrimer-probe setsAssaysLow sensitivityCritical needAnalytical sensitivity
2019
RIG-I Selectively Discriminates against 5′-Monophosphate RNA
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Selectively Discriminates against 5′-Monophosphate RNA. Cell Reports 2019, 26: 2019-2027.e4. PMID: 30784585, DOI: 10.1016/j.celrep.2019.01.107.Peer-Reviewed Original Research
2017
Zika virus causes testicular atrophy
Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ, Hastings AK, Homer RJ, Iwasaki A, Fikrig E. Zika virus causes testicular atrophy. Science Advances 2017, 3: e1602899. PMID: 28261663, PMCID: PMC5321463, DOI: 10.1126/sciadv.1602899.Peer-Reviewed Original ResearchConceptsZika virusTesticular atrophyAcute viremic phaseZIKV-infected miceMosquito-borne flavivirusTestosterone-producing Leydig cellsProgressive testicular atrophyZIKV persistenceFetal infectionViremic phaseNeonatal abnormalitiesSerum testosteroneZIKV infectionNeurological dysfunctionSubcutaneous injectionZIKV replicationLeydig cellsVirus replicationVertical transmissionEpithelial cellsMiceViral RNAReproductive deficienciesAtrophyMale fertility
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 functionCells
2013
Different routes to the same destination
Hayashi K, Iwasaki A. Different routes to the same destination. ELife 2013, 2: e00572. PMID: 23426937, PMCID: PMC3576710, DOI: 10.7554/elife.00572.Peer-Reviewed Original Research
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
2004
Recognition 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