2024
A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses
Yang Y, Treger R, Hernandez-Bird J, Lu P, Mao T, Iwasaki A. A B cell screen against endogenous retroviruses identifies glycan-reactive IgM that recognizes a broad array of enveloped viruses. Science Immunology 2024, 9: eadd6608. PMID: 39514636, DOI: 10.1126/sciimmunol.add6608.Peer-Reviewed Original ResearchConceptsB-1 cellsB cell-deficient miceEndogenous retrovirusesEnveloped virusesNatural IgM antibodiesGermline-encoded antibodiesNaive miceInnate antiviral mechanismsGenetic invadersB cellsVertebrate genomesNatural antibody repertoireRepertoire profilingSurface antigensInfectious endogenous retrovirusIgM antibodiesSelf-proteinsComplement pathwayAntibody repertoireAntibodiesMiceRetrovirusesVirusSensor stimulationGlycoprotein
2022
Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, O'Dea MR, Dutton S, Shamardani K, Nwangwu K, Mancusi R, Yalçın B, Taylor KR, Acosta-Alvarez L, Malacon K, Keough MB, Ni L, Woo PJ, Contreras-Esquivel D, Toland AMS, Gehlhausen JR, Klein J, Takahashi T, Silva J, Israelow B, Lucas C, Mao T, Peña-Hernández MA, Tabachnikova A, Homer RJ, Tabacof L, Tosto-Mancuso J, Breyman E, Kontorovich A, McCarthy D, Quezado M, Vogel H, Hefti MM, Perl DP, Liddelow S, Folkerth R, Putrino D, Nath A, Iwasaki A, Monje M. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 2022, 185: 2452-2468.e16. PMID: 35768006, PMCID: PMC9189143, DOI: 10.1016/j.cell.2022.06.008.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMicroglial reactivityCognitive impairmentCSF cytokines/chemokinesCytokines/chemokinesSARS-CoV-2Early time pointsCCL11 levelsMild COVIDRespiratory influenzaHippocampal neurogenesisOligodendrocyte lossHippocampal pathologyMyelin lossNeurological symptomsImpaired neurogenesisCOVID survivorsNeurobiological effectsNeural dysregulationMyelin dysregulationCCL11Neural cellsTime pointsNeurogenesisMiceGlycan-specific B-1 cells mediate blockade of endogenous retroviruses emergence through recognition of conserved glycan epitopes
Yang Y, Treger R, Hernandez-Bird J, Iwasaki A. Glycan-specific B-1 cells mediate blockade of endogenous retroviruses emergence through recognition of conserved glycan epitopes. The Journal Of Immunology 2022, 208: 126.31-126.31. DOI: 10.4049/jimmunol.208.supp.126.31.Peer-Reviewed Original ResearchB-1 cellsB cell populationsB cellsEndogenous retrovirusesCell-intrinsic controlNatural antibodiesImmunodeficient miceUnimmunized miceGlycan-specific antibodiesClonal repertoirePleural cavityRepertoire profilingViral antigensBlockadeComplement pathwayVH genesCell compartmentAntibodiesGlycan epitopesMiceRetrovirusesAbstract Endogenous retrovirusesEpitopesSensor stimulationCellsEndogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Jayewickreme R, Mao T, Philbrick W, Kong Y, Treger RS, Lu P, Rakib T, Dong H, Dang-Lawson M, Guild WA, Lau TJ, Iwasaki A, Tokuyama M. Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease. Frontiers In Immunology 2022, 12: 758721. PMID: 35058919, PMCID: PMC8764156, DOI: 10.3389/fimmu.2021.758721.Peer-Reviewed Original ResearchConceptsHSV-2 infectionHSV-2 diseaseHerpes simplex virus type 2 infectionSimplex virus type 2 infectionEnhanced type I interferonIntravaginal HSV-2 infectionVaginal HSV-2 infectionVirus type 2 infectionEndogenous retrovirusesReceptor-deficient miceType 2 infectionHigh systemic levelsWildtype C57BL/6 miceType I interferonTLR7-/- miceC57BL/6 miceInfectious endogenous retrovirusDeficient miceIntravaginal applicationAntiviral immunityI interferonVaginal tissueDetrimental functionsTLR7Mice
2021
Glycan-reactive natural antibodies mediate blockade of endogenous retroviruses emergence
Yang Y, Treger R, Hernandez-Bird J, Iwasaki A. Glycan-reactive natural antibodies mediate blockade of endogenous retroviruses emergence. The Journal Of Immunology 2021, 206: 114.09-114.09. DOI: 10.4049/jimmunol.206.supp.114.09.Peer-Reviewed Original ResearchB-1 cellsB cell populationsB cellsNatural antibodiesEndogenous retrovirusesCell-intrinsic controlImmunodeficient miceSelf-antigensUnimmunized miceFetal haematopoiesisGlycan-specific antibodiesClonal repertoirePleural cavityRepertoire profilingViral antigensBlockadeComplement pathwayVH genesCell compartmentAntibodiesCell-specificAbstract Endogenous retrovirusesMiceGenetic invadersVertebrate genomes
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMiceEnvironmental Conditioning and Aerosol Infection of Mice.
Kudo E, Iwasaki A. Environmental Conditioning and Aerosol Infection of Mice. Bio-protocol 2020, 10: e3592. PMID: 33659558, PMCID: PMC7842367, DOI: 10.21769/bioprotoc.3592.Peer-Reviewed Original ResearchCutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy.
Gopinath S, Lu P, Iwasaki A. Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy. The Journal Of Immunology 2020, 204: 1703-1707. PMID: 32122994, DOI: 10.4049/jimmunol.1900462.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsGenital herpes infectionMemory T cellsT cellsHerpes infectionVirus-specific effector T cellsVaginal applicationTopical vaginal applicationCD8 T cellsEffector T cellsProtective immune responseSingle topical applicationTopical aminoglycosidesGenital mucosaChemokine expressionVaccine strategiesImmune responseVaginal mucosaTopical applicationBarrier tissuesMiceRobust activationAminoglycoside antibioticsMucosaInfection
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 expressionHumansExpressionAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserumThe Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV
Treger RS, Pope SD, Kong Y, Tokuyama M, Taura M, Iwasaki A. The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV. Immunity 2019, 50: 334-347.e9. PMID: 30709743, PMCID: PMC6382577, DOI: 10.1016/j.immuni.2018.12.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEndogenous RetrovirusesGene Expression RegulationGenetic Predisposition to DiseaseGlycoproteinsHEK293 CellsHumansLupus Erythematosus, SystemicLupus NephritisMiceMice, 129 StrainMice, Inbred C57BLMice, Inbred NZBMice, KnockoutMolecular ChaperonesNuclear ProteinsRepressor Proteins
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 activatorsMiceInterferonGenesRNAPublisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice
Jurado K, Yockey L, Wong P, Lee S, Huttner A, Iwasaki A. Publisher Correction: Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nature Microbiology 2018, 3: 255-255. DOI: 10.1038/s41564-017-0101-7.Peer-Reviewed Original Research
2017
Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice
Uraki R, Jurado KA, Hwang J, Szigeti-Buck K, Horvath TL, Iwasaki A, Fikrig E. Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice. The Journal Of Infectious Diseases 2017, 215: 1720-1724. PMID: 28472297, PMCID: PMC5853330, DOI: 10.1093/infdis/jix204.Peer-Reviewed Original ResearchConceptsZika virusSexual transmissionWeight of fetusesFetal growth restrictionNaive female miceType I interferon receptorEmbryonic day 18.5Female miceGrowth restrictionMale miceOcular deformityMosquito bitesControl groupDay 18.5Fetal abnormalitiesSexual contactInterferon receptorMiceFetusesInfected malesVirusDeformityAbnormalitiesReceptorsTAM Receptors Are Not Required for Zika Virus Infection in Mice
Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R, Gaitsch HF, Parnell LA, Cao B, Mysorekar IU, Rothlin CV, Fikrig E, Diamond MS, Iwasaki A. TAM Receptors Are Not Required for Zika Virus Infection in Mice. Cell Reports 2017, 19: 558-568. PMID: 28423319, PMCID: PMC5485843, DOI: 10.1016/j.celrep.2017.03.058.Peer-Reviewed Original ResearchConceptsTAM receptorsZika virusAbsence of IFNARGlobal public health concernNon-pregnant miceZika virus infectionAdult female micePublic health concernZIKV entryZIKV infectionFemale miceViral inoculationZIKV replicationMertk (TAM) receptorsYoung miceVirus infectionEntry receptorViral titersViral replicationCell tropismInfectionHealth concernMiceAxlReceptorsZika 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
2016
CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens
Kumamoto Y, Hirai T, Wong PW, Kaplan DH, Iwasaki A. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. ELife 2016, 5: e17979. PMID: 27657168, PMCID: PMC5033605, DOI: 10.7554/elife.17979.Peer-Reviewed Original ResearchDendritic cellsAntibody responsePD-L1Protein antigensBlocking PD-1Follicular helper cellsPD-1 ligandsStrong antibody responseWild-type miceGerminal center B cellsTfh cellsPD-1Cell primingIgG responsesHelper cellsPD-L2Autoantibody generationSuccessful vaccineCD301bB cellsTransient depletionAntigenMiceAntibodiesNovel regulatory mechanismCD301b+ Macrophages Are Essential for Effective Skin Wound Healing
Shook B, Xiao E, Kumamoto Y, Iwasaki A, Horsley V. CD301b+ Macrophages Are Essential for Effective Skin Wound Healing. Journal Of Investigative Dermatology 2016, 136: 1885-1891. PMID: 27287183, PMCID: PMC5727894, DOI: 10.1016/j.jid.2016.05.107.Peer-Reviewed Original ResearchConceptsSkin wound healingBarrier functionEssential inflammatory cellsAnti-inflammatory macrophagesWound healingSkin barrier functionSubpopulation of macrophagesEarly regenerative stageMultiple myeloid lineagesInflammatory cellsSyngeneic miceWound healing defectsMyeloid cellsCutaneous repairReparative processesSelective depletionPhenotype switchMacrophagesMyeloid lineageMiceMultiple cell typesHealingCD301bHealing defectsSkin repairAntiviral responses of inbred mice
Iwasaki A. Antiviral responses of inbred mice. Nature Reviews Immunology 2016, 16: 339-339. PMID: 27108522, DOI: 10.1038/nri.2016.44.Peer-Reviewed Original ResearchMx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza