2015
Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism
Thakar J, Hartmann BM, Marjanovic N, Sealfon SC, Kleinstein SH. Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism. BMC Immunology 2015, 16: 46. PMID: 26272204, PMCID: PMC4536893, DOI: 10.1186/s12865-015-0107-y.Peer-Reviewed Original ResearchConceptsTranscription factor activityImmune antagonismExpression profilesGenome-wide expression profilesGenome-wide transcriptional profiling dataFactor activityGenome-wide transcriptional profilesTranscription factor SATB1DNA-binding sitesTranscriptional profiling dataHost-pathogen interactionsGene expression profilesISGF3 activityTranscriptional responseTranscription factorsTranscriptional profilesHost interactionsProfiling dataApplication of betaNovel effectMechanistic insightsInfected cellsInfluenza A virusesMechanistic differencesNewcastle disease virusHuman 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
Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression
Bolen CR, Ding S, Robek MD, Kleinstein SH. Dynamic expression profiling of type I and type III interferon‐stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology 2014, 59: 1262-1272. PMID: 23929627, PMCID: PMC3938553, DOI: 10.1002/hep.26657.Peer-Reviewed Original ResearchConceptsGene expressionExpression profilingIndividual interferonMicroarray-based gene expression profilingDynamic expression profilingGene expression profilingSimilar signaling cascadesPotential specific rolesPromoter analysisTranscriptional responseHuh7 hepatoma cellsGene inductionExpression hierarchySignaling cascadesIFN-α signalingAntiviral stateNegative feedback mechanismType IPrimary human hepatocytesHepatoma cellsISG inductionSpecific roleGenesInterferon-stimulated gene inductionSuperior clinical activity
2013
Overcoming NS1-Mediated Immune Antagonism Involves Both Interferon-Dependent and Independent Mechanisms
Thakar J, Schmid S, Duke JL, García-Sastre A, Kleinstein SH. Overcoming NS1-Mediated Immune Antagonism Involves Both Interferon-Dependent and Independent Mechanisms. Journal Of Interferon & Cytokine Research 2013, 33: 700-708. PMID: 23772952, PMCID: PMC3814816, DOI: 10.1089/jir.2012.0113.Peer-Reviewed Original ResearchConceptsNonstructural protein 1Immune antagonismWild-type C57BL/6 miceIFN-independent mechanismsInduction of IFNCritical antiviral cytokinesInduction of IFNB1Host interferon responseEffective IFNInterferon-DependentC57BL/6 miceAntiviral cytokinesInfluenza A.IFNImmune systemInterferon responseFlu strainImmune antagonistsProtein 1H postinfectionIndependent mechanismsInfectionMiceAntagonismIFNB1
2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearanceThe 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
2008
Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*
Pagliaccetti NE, Eduardo R, Kleinstein SH, Mu XJ, Bandi P, Robek MD. Interleukin-29 Functions Cooperatively with Interferon to Induce Antiviral Gene Expression and Inhibit Hepatitis C Virus Replication*. Journal Of Biological Chemistry 2008, 283: 30079-30089. PMID: 18757365, PMCID: PMC2662072, DOI: 10.1074/jbc.m804296200.Peer-Reviewed Original ResearchConceptsAntiviral gene expressionIFN-alpha/betaIL-29IFN-alphaVirus replicationIFN-gammaInhibits Hepatitis C Virus ReplicationCritical innate immune responseAntiviral activityHepatitis C virus replicationChronic viral infectionsC virus replicationGreater antiviral activityInnate immune responseIFN-gamma combinationHepatitis CGene expressionCellular antiviral responseCytokines interleukinHCV replicationImmune responseViral infectionIndividual cytokinesVesicular stomatitis virusAntiviral response