2023
Early cellular and molecular signatures correlate with severity of West Nile virus infection
Lee H, Zhao Y, Fleming I, Mehta S, Wang X, Vander Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.Peer-Reviewed Original ResearchWest Nile virusEffective anti-viral responseInnate immune cell typesWest Nile virus infectionPro-inflammatory markersAcute time pointsImmune cell typesAnti-viral responseMolecular signaturesHost cellular activitiesAcute infectionAsymptomatic donorsPeripheral bloodSevere infectionsVirus infectionImmune responseSevere casesCell activityIll individualsSerum proteomicsInfectionInfection severityHigh expressionTime pointsNile virus
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionComparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses
Nudelman I, Kudrin D, Nudelman G, Deshpande R, Hartmann BM, Kleinstein SH, Myers CL, Sealfon SC, Zaslavsky E. Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses. Frontiers In Immunology 2021, 12: 691758. PMID: 34335598, PMCID: PMC8317020, DOI: 10.3389/fimmu.2021.691758.Peer-Reviewed Original ResearchConceptsDifferent virus strainsHost responseVirus strainsInfluenza virus infectionSerious global health threatInfluenza H1N1 virusCommon core responseGlobal health threatH1N1 virusVirus infectionImmune responseInfluenza strainsTherapeutic targetInfluenza virusHealth threatInfectionActivation patternsDifferent virusesDifferent temporal patternsVirusHost cellsFunctional networksFunctional pathwaysSame cellular pathwaysCellular pathways
2020
CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response
Lu Y, Jiang R, Freyn AW, Wang J, Strohmeier S, Lederer K, Locci M, Zhao H, Angeletti D, O’Connor K, Kleinstein SH, Nachbagauer R, Craft J. CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response. Journal Of Experimental Medicine 2020, 218: e20200547. PMID: 33326020, PMCID: PMC7748821, DOI: 10.1084/jem.20200547.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigensB-LymphocytesCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanInfluenzavirus BIntegrasesMice, Inbred C57BLOrthomyxoviridae InfectionsReceptors, Antigen, B-CellSpecies SpecificityT-Lymphocytes, RegulatoryVaccinationConceptsB cell responsesGerminal center B cell responsesFollicular regulatory T cellsRegulatory T cellsTfr cellsCell responsesT cellsViral challengeHumoral memoryVirus-specific B cell responsesAntigen-specific B cell responsesFollicular helper T cellsHA stalk regionHelper T cellsInfluenza virus infectionGerminal center developmentAntibody responsePlasma cellsVirus infectionImmunization modelAntibody productionBCR repertoireInfluenza virusRepeated exposureInfluenza virus glycoproteins
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesHuman Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses
Hartmann BM, Thakar J, Albrecht RA, Avey S, Zaslavsky E, Marjanovic N, Chikina M, Fribourg M, Hayot F, Schmolke M, Meng H, Wetmur J, García-Sastre A, Kleinstein SH, Sealfon SC. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses. Journal Of Virology 2015, 89: 10190-10205. PMID: 26223639, PMCID: PMC4580178, DOI: 10.1128/jvi.01523-15.Peer-Reviewed Original ResearchMeSH KeywordsAntigenic VariationDendritic CellsEuropeGene Expression ProfilingGene Expression RegulationHistory, 20th CenturyHistory, 21st CenturyHost-Pathogen InteractionsHumansInfluenza A Virus, H1N1 SubtypeInfluenza Pandemic, 1918-1919Influenza, HumanInterferonsMolecular EpidemiologyNF-kappa BPandemicsReassortant VirusesRecombination, GeneticSeasonsSignal TransductionTime FactorsUnited StatesConceptsHuman dendritic cellsDendritic cellsImmune responseInfluenza virusSeasonal strainsNF-κBSeasonal H1N1 influenza virusHuman influenza virus infectionH1N1 influenza strainInterferon-stimulated gene responseSeasonal influenza virusesInfluenza virus infectionH1N1 influenza virusStrain-dependent differencesClinical severityVirus infectionInfluenza strainsAntiviral programViral infectionPandemic strainsHost responseAntigenic driftInfectionH postinfectionSelective induction
2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cells
2013
Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis
Querol L, Clark PL, Bailey MA, Cotsapas C, Cross AH, Hafler DA, Kleinstein SH, Lee JY, Yaari G, Willis SN, O'Connor KC. Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis. Neurology 2013, 81: 956-963. PMID: 23921886, PMCID: PMC3888197, DOI: 10.1212/wnl.0b013e3182a43b48.Peer-Reviewed Original ResearchConceptsCSF of patientsMultiple sclerosisNeurologic diseaseEpstein-Barr virus infectionImmunoglobulin GElevated immunoglobulin GInflammatory neurologic diseasesSubset of patientsLarger validation cohortRecombination signal binding proteinImmunoglobulin kappa J regionCSF autoantibodiesValidation cohortControl subjectsSerum reactivityAutoantigen candidatesHigh prevalenceVirus infectionPatientsAutoantibodiesCSFSclerosisArray-based profilingDiseaseELISA
2012
The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response
Bolen CR, Robek MD, Brodsky L, Schulz V, Lim JK, Taylor MW, Kleinstein SH. The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response. Journal Of Interferon & Cytokine Research 2012, 33: 15-23. PMID: 23067362, PMCID: PMC3539252, DOI: 10.1089/jir.2012.0037.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHCV patientsHealthy volunteersChronic hepatitis C virus (HCV) infectionChronic hepatitis C virusInfected individualsTreatment-naïve HCV patientsHepatitis C virus infectionBlood transcriptional profilesBlood transcriptional signaturesC virus infectionChronic HCV infectionOngoing immune responseBlood mononuclear cellsHepatitis C virusBlood transcriptional profilingDrug treatment responseHCV infectionSubset of IFNMononuclear cellsC virusIFN signatureHealthy controlsTreatment responseVirus infection